Volume 13 Issue 12
Dec.  2022
Turn off MathJax
Article Contents
Linchong Sun, Huafeng Zhang, Ping Gao. Metabolic reprogramming and epigenetic modifications on the path to cancer[J]. Protein&Cell, 2022, 13(12): 877-919. doi: 10.1007/s13238-021-00846-7
Citation: Linchong Sun, Huafeng Zhang, Ping Gao. Metabolic reprogramming and epigenetic modifications on the path to cancer[J]. Protein&Cell, 2022, 13(12): 877-919. doi: 10.1007/s13238-021-00846-7

Metabolic reprogramming and epigenetic modifications on the path to cancer

doi: 10.1007/s13238-021-00846-7

D Program of China (2018YFA0107103, 2018YFA0800300, 2017YFA0205600), the Chinese Academy of Sciences (XDB39000000), the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2017ZT07S054), Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (2018GZR110102001), and the Fundamental Research Funds for the Central Universities (YD2070002008, 2020ZYGXZR038).

This work was supported by National Natural Science Foundation of China (91957203, 81930083, 81874060, 81821001), National Key R&

  • Received Date: 2021-01-13
  • Rev Recd Date: 2021-04-02
  • Metabolic rewiring and epigenetic remodeling, which are closely linked and reciprocally regulate each other, are among the well-known cancer hallmarks. Recent evidence suggests that many metabolites serve as substrates or cofactors of chromatin-modifying enzymes as a consequence of the translocation or spatial regionalization of enzymes or metabolites. Various metabolic alterations and epigenetic modifications also reportedly drive immune escape or impede immunosurveillance within certain contexts, playing important roles in tumor progression. In this review, we focus on how metabolic reprogramming of tumor cells and immune cells reshapes epigenetic alterations, in particular the acetylation and methylation of histone proteins and DNA. We also discuss other eminent metabolic modifications such as, succinylation, hydroxybutyrylation, and lactylation, and update the current advances in metabolism- and epigenetic modification-based therapeutic prospects in cancer.
  • loading
  • [1]
    Abmayr SM, Workman JL (2019) Histone lysine de-beta-hydroxybutyrylation by SIRT3. Cell Res 29:694-695
    Adams RR, Maiato H, Earnshaw WC, Carmena M (2001) Essential roles of Drosophila inner centromere protein (INCENP) and aurora B in histone H3 phosphorylation, metaphase chromosome alignment, kinetochore disjunction, and chromosome segregation. J Cell Biol 153:865-879
    Alarcon C, Wicksteed B, Prentki M, Corkey BE, Rhodes CJ (2002) Succinate is a preferential metabolic stimulus-coupling signal for glucose-induced proinsulin biosynthesis translation. Diabetes 51:2496-2504
    Albrengues J, Shields MA, Ng D, Park CG, Ambrico A, Poindexter ME, Upadhyay P, Uyeminami DL, Pommier A, Kuttner V et al (2018) Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science 361:eaao4227
    Alleyn M, Breitzig M, Lockey R, Kolliputi N (2018) The dawn of succinylation:a posttranslational modification. Am J Physiol Cell Physiol 314:C228-C232
    Allison DF, Wamsley J, Kumar M, Li D, Gray LG, Hart GW, Jones DR, Mayo MW (2012) Modification of RelA by O-linked N-acetylglucosamine links glucose metabolism to NF-kappa B acetylation and transcription. Proc Natl Acad Sci USA 109:16888-16893
    Altman BJ, Stine ZE, Dang CV (2016) From Krebs to clinic:glutamine metabolism to cancer therapy. Nat Rev Cancer 16:619-634
    Alvarez-Nunez F, Bussaglia E, Mauricio D, Ybarra J, Vilar M, Lerma E, de Leiva A, Matias-Guju X, Grp TNS (2006) PTEN promoter methylation in sporadic thyroid carcinomas. Thyroid 16:17-23
    Amato RJ (2007) Inhibition of DNA methylation by antisense oligonucleotide MG98 as cancer therapy. Clin Genitourinary Cancer 5:422-426
    Anand R, Marmorstein R (2007) Structure and mechanism of lysine-specific demethylase enzymes. J Biol Chem 282:35425-35429
    Anest V, Hanson JL, Cogswell PC, Steinbrecher KA, Strahl BD, Baldwin AS (2003) A nucleosomal function for IkappaB kinase-alpha in NF-kappaB-dependent gene expression. Nature 423:659-663
    Ariyannur PS, Moffett JR, Madhavarao CN, Arun P, Vishnu N, Jacobowitz DM, Hallows WC, Denu JM, Namboodiri AMA (2010) Nuclear-cytoplasmic localization of acetyl coenzyme A synthetase-1 in the rat brain. J Comp Neurol 518:2952-2977
    Asaga H, Yamada M, Senshu T (1998) Selective deimination of vimentin in calcium ionophore-induced apoptosis of mouse peritoneal macrophages. Biochem Biophys Res Commun 243:641-646
    Astuti D, Latif F, Dallol A, Dahia PLM, Douglas F, George E, Skoldberg F, Husebye ES, Eng C, Maher ER (2001) Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am J Hum Genet 69:49-54
    Audia JE, Campbell RM (2016) Histone Modifications and Cancer. Cold Spring Harb Perspect Biol 8:
    Badgley MA, Kremer DM, Maurer HC, DelGiorno KE, Lee HJ, Purohit V, Sagalovskiy IR, Ma A, Kapilian J, Firl CEM et al (2020) Cysteine depletion induces pancreatic tumor ferroptosis in mice. Science 368:85-89
    Ballantyne CM, Davidson MH, Macdougall DE, Bays HE, Dicarlo LA, Rosenberg NL, Margulies J, Newton RS (2013) Efficacy and safety of a novel dual modulator of adenosine triphosphate-citrate lyase and adenosine monophosphate-activated protein kinase in patients with hypercholesterolemia:results of a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. J Am Coll Cardiol 62:1154-1162
    Bambouskova M, Gorvel L, Lampropoulou V, Sergushichev A, Loginicheva E, Johnson K, Korenfeld D, Mathyer ME, Kim H, Huang LH et al (2018) Electrophilic properties of itaconate and derivatives regulate the IkappaBzeta-ATF3 inflammatory axis. Nature 556:501-504
    Bandukwala HS, Gagnon J, Togher S, Greenbaum JA, Lamperti ED, Parr NJ, Molesworth AM, Smithers N, Lee K, Witherington J et al (2012) Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors. Proc Natl Acad Sci USA 109:14532-14537
    Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21:381-395
    Barlesi F, Giaccone G, Gallegos-Ruiz MI, Loundou A, Span SW, Lefesvre P, Kruyt FA, Rodriguez JA (2007) Global histone modifications predict prognosis of resected non small-cell lung cancer. J Clin Oncol 25:4358-4364
    Yu WY, Chory EJ, Wernimont AK, Tempel W, Scopton A, Federation A, Marineau JJ, Qi J, Barsyte-Lovejoy, D, Yi JN et al (2012) Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors. Nat Commun 3
    Basappa J, Citir M, Zhang Q, Wang HY, Liu X, Melnikov O, Yahya H, Stein F, Muller R, Traynor-Kaplan A et al (2020) ACLY is the novel signaling target of PIP2/PIP3 and Lyn in acute myeloid leukemia. Heliyon 6:
    Bayley JP, Kunst HPM, Cascon A, Sampietro ML, Gaal J, Korpershoek E, Hinojar-Gutierrez A, Timmers HJLM, Hoefsloot LH, Hermsen MA et al (2010) SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma. Lancet Oncol 11:366-372
    Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, van der Mey A, Taschner PEM, Rubinstein WS, Myers EN et al (2000) Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287:848-851
    Becker-Kettern J, Paczia N, Conrotte JF, Kay DP, Guignard C, Jung PP, Linster CL (2016) Saccharomyces cerevisiae forms d-2-hydroxyglutarate and couples its degradation to d-lactate formation via a cytosolic transhydrogenase. J Biol Chem 291:6036-6058
    Bender S, Tang Y, Lindroth AM, Hovestadt V, Jones DT, Kool M, Zapatka M, Northcott PA, Sturm D, Wang W et al (2013) Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cancer Cell 24:660-672
    Berger-Achituv S, Brinkmann V, Abu Abed U, Kuhn LI, Ben-Ezra J, Elhasid R, Zychlinsky A (2013) A proposed role for neutrophil extracellular traps in cancer immunoediting. Front Immunol 4
    Bergman Y, Cedar H (2013) DNA methylation dynamics in health and disease. Nat Struct Mol Biol 20:274-281
    Bharathi SS, Zhang YX, Mohsen AW, Uppala R, Balasubramani M, Schreiber E, Uechi G, Beck ME, Rardin MJ, Vockley J et al (2013) Sirtuin 3 (SIRT3) protein regulates long-chain Acyl-CoA dehydrogenase by deacetylating conserved lysines near the active site. J Biol Chem 288:33837-33847
    Bian Y, Li W, Kremer DM, Sajjakulnukit P, Li S, Crespo J, Nwosu ZC, Zhang L, Czerwonka A, Pawlowska A et al (2020) Cancer SLC43A2 alters T cell methionine metabolism and histone methylation. Nature
    Bianco-Miotto T, Chiam K, Buchanan G, Jindal S, Day TK, Thomas M, Pickering MA, O'Loughlin MA, Ryan NK, Raymond WA et al (2010) Global levels of specific histone modifications and an epigenetic gene signature predict prostate cancer progression and development. Cancer Epidemiol Biomarkers Prev 19:2611-2622
    Branco AF, Ferreira A, Simoes RF, Magalhaes-Novais S, Zehowski C, Cope E, Silva AM, Pereira D, Sardao VA, Cunha-Oliveira T (2016) Ketogenic diets:from cancer to mitochondrial diseases and beyond. Eur J Clin Invest 46:285-298
    Breillout F, Hadida F, Echinard-Garin P, Lascaux V, Poupon MF (1987) Decreased rat rhabdomyosarcoma pulmonary metastases in response to a low methionine diet. Anticancer Res 7:861-867
    Brueckner B, Boy RG, Siedlecki P, Musch T, Kliem HC, Zielenkiewicz P, Suhai S, Wiessler M, Lyko F (2005) Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases. Cancer Res 65:6305-6311
    Bulusu V, Tumanov S, Michalopoulou E, van den Broek NJ, MacKay G, Nixon C, Dhayade S, Schug ZT, Voorde JV, Blyth K et al (2017) Acetate recapturing by nuclear acetyl-CoA synthetase 2 prevents loss of histone acetylation during oxygen and serum limitation. Cell Rep 18:647-658
    Bungard D, Fuerth BJ, Zeng PY, Faubert B, Maas NL, Viollet B, Carling D, Thompson CB, Jones RG, Berger SL (2010) Signaling kinase AMPK activates stress-promoted transcription via histone H2B phosphorylation. Science 329:1201-1205
    Caballero F, Fernandez A, Matias N, Martinez L, Fucho R, Elena M, Caballeria J, Morales A, Fernandez-Checa JC, Garcia-Ruiz C (2010) Specific contribution of methionine and choline in nutritional nonalcoholic steatohepatitis:impact on mitochondrial S-adenosyl-L-methionine and glutathione. J Biol Chem 285:18528-18536
    Cai L, Sutter BM, Li B, Tu BP (2011) Acetyl-CoA induces cell growth and proliferation by promoting the acetylation of histones at growth genes. Mol Cell 42:426-437
    Cairns RA, Mak TW (2013) Oncogenic isocitrate dehydrogenase mutations:mechanisms, models, and clinical opportunities. Cancer Discov 3:730-741
    Cairns RA, Mak TW (2017) S-2HG is an immunometabolite that shapes the T-cell response. Cell Death Differ 24:195-196
    Candido EP, Reeves R, Davie JR (1978) Sodium butyrate inhibits histone deacetylation in cultured cells. Cell 14:105-113
    Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, Jones RS, Zhang Y (2002) Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298:1039-1043
    Caprariello AV, Rogers JA, Morgan ML, Hoghooghi V, Plemel JR, Koebel A, Tsutsui S, Dunn JF, Kotra LP, Ousman SS et al (2018) Biochemically altered myelin triggers autoimmune demyelination. Proc Natl Acad Sci USA 115:5528-5533
    Carey BW, Finley LWS, Cross JR, Allis CD, Thompson CB (2015) Intracellular alpha-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature 518:413-416
    Carrer A, Trefely S, Zhao S, Campbell SL, Norgard RJ, Schultz KC, Sidoli S, Parris JLD, Affronti HC, Sivanand S et al (2019) Acetyl-CoA metabolism supports multistep pancreatic tumorigenesis. Cancer Discov 9:416-435
    Carrico C, Meyer JG, He W, Gibson BW, Verdin E (2018) The mitochondrial acylome emerges:proteomics, regulation by sirtuins, and metabolic and disease implications. Cell Metab 27:497-512
    Carrillo-Vico A, Leech MD, Anderton SM (2010) Contribution of myelin autoantigen citrullination to T cell autoaggression in the central nervous system. J Immunol 184:2839-2846
    Ceccacci E, Minucci S (2016) Inhibition of histone deacetylases in cancer therapy:lessons from leukaemia. Br J Cancer 114:605-611
    Chan KM, Fang D, Gan H, Hashizume R, Yu C, Schroeder M, Gupta N, Mueller S, James CD, Jenkins R et al (2013) The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression. Genes Dev 27:985-990
    Chang XT, Han JX, Pang L, Zhao Y, Yang Y, Shen ZL (2009) Increased PADI4 expression in blood and tissues of patients with malignant tumors. BMC Cancer 9
    Chang XT, Hou XL, Pan JH, Fang KH, Wang L, Han JX (2011) Investigating the pathogenic role of PADI4 in oesophageal cancer. Int J Biol Sci 7:769-781
    Chen LL, Xiong Y (2020) Tumour metabolites hinder DNA repair. Nature 582:492-494
    Chen L, Deshpande AJ, Banka D, Bernt KM, Dias S, Buske C, Olhava EJ, Daigle SR, Richon VM, Pollock RM et al (2013a) Abrogation of MLL-AF10 and CALM-AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l. Leukemia 27:813-822
    Chen Q, Chen Y, Bian C, Fujiki R, Yu X (2013b) TET2 promotes histone O-GlcNAcylation during gene transcription. Nature 493:561-564
    Chen L, Miao ZG, Xu XS (2017) beta-hydroxybutyrate alleviates depressive behaviors in mice possibly by increasing the histone3-lysine9-beta-hydroxybutyrylation. Biochem Biophys Res Commun 490:117-122
    Chen J, Guccini I, Di Mitri D, Brina D, Revandkar A, Sarti M, Pasquini E, Alajati A, Pinton S, Losa M et al (2018a) Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer. Nat Genet 50:219-228
    Chen XF, Tian MX, Sun RQ, Zhang ML, Zhou LS, Jin L, Chen LL, Zhou WJ, Duan KL, Chen YJ et al (2018b) SIRT5 inhibits peroxisomal ACOX1 to prevent oxidative damage and is downregulated in liver cancer. Embo Rep 19.
    Cheng Y, He C, Wang MN, Ma XL, Mo F, Yang SY, Han JH, Wei XW (2019) Targeting epigenetic regulators for cancer therapy:mechanisms and advances in clinical trials. Signal Transduction Targeted Ther 4
    Cheon YP, Xu XP, Bagchi MK, Bagchi IC (2003) Immune-responsive gene 1 is a novel target of progesterone receptor and plays a critical role during implantation in the mouse. Endocrinology 144:5623-5630
    Chisolm DA, Weinmann AS (2018) Connections between metabolism and epigenetics in programming cellular differentiation. Annu Rev Immunol 36(36):221-246
    Choi HS, Choi BY, Cho YY, Mizuno H, Kang BS, Bode AM, Dong ZG (2005) Phosphorylation of histone H3 at serine 10 is indispensable for neoplastic cell transformation. Cancer Res 65:5818-5827
    Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325:834-840
    Choudhary C, Weinert BT, Nishida Y, Verdin E, Mann M (2014) The growing landscape of lysine acetylation links metabolism and cell signalling. Nat Rev Mol Cell Biol 15:536-550
    Chowdhury R, Yeoh KK, Tian YM, Hillringhaus L, Bagg EA, Rose NR, Leung IKH, Li XS, Woon ECY, Yang M et al (2011) The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep 12:463-469
    Christman JK (2002) 5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation:mechanistic studies and their implications for cancer therapy. Oncogene 21:5483-5495
    Christophorou MA, Castelo-Branco G, Halley-Stott RP, Oliveira CS, Loos R, Radzisheuskaya A, Mowen KA, Bertone P, Silva JCR, Zernicka-Goetz M et al (2014) Citrullination regulates pluripotency and histone H1 binding to chromatin. Nature 507:104-108
    Chu CS, Lo PW, Yeh YH, Hsu PH, Peng SH, Teng YC, Kang ML, Wong CH, Juan LJ (2014) O-GlcNAcylation regulates EZH2 protein stability and function. Proc Natl Acad Sci USA 111:1355-1360
    Chu QS, Sangha R, Spratlin J, Vos LJ, Mackey JR, McEwan AJ, Venner P, Michelakis ED (2015) A phase I open-labeled, single-arm, dose-escalation, study of dichloroacetate (DCA) in patients with advanced solid tumors. Invest New Drugs 33:603-610
    Chuang JC, Yoo CB, Kwan JM, Li TWH, Liang GN, Yang AS, Jones PA (2005) Comparison of biological effects of non-nucleoside DNA methylation inhibitors versus 5-aza-2'-deoxycytidine. Mol Cancer Ther 4:1515-1520
    Chuang JC, Warner SL, Vollmer D, Vankayalapati H, Redkar S, Bearss DJ, Qiu XN, Yoo CB, Jones PA (2010) S110, a 5-Aza-2'-deoxycytidine-containing dinucleotide, is an effective DNA methylation inhibitor in vivo and can reduce tumor growth. Mol Cancer Ther 9:1443-1450
    Chung C, Sweha SR, Pratt D, Tamrazi B, Panwalkar P, Banda A, Bayliss J, Hawes D, Yang F, Lee HJ et al (2020) Integrated metabolic and epigenomic reprograming by H3K27M mutations in diffuse intrinsic pontine gliomas. Cancer Cell 38(334-349):
    Chypre M, Zaidi N, Smans K (2012) ATP-citrate lyase:a mini-review. Biochem Biophys Res Commun 422:1-4
    Cohen I, Poreba E, Kamieniarz K, Schneider R (2011) Histone modifiers in cancer:friends or foes? Genes Cancer 2:631-647
    Comerford SA, Huang Z, Du X, Wang Y, Cai L, Witkiewicz AK, Walters H, Tantawy MN, Fu A, Manning HC et al (2014) Acetate dependence of tumors. Cell 159:1591-1602
    Cook PJ, Ju BG, Telese F, Wang X, Glass CK, Rosenfeld MG (2009) Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions. Nature 458:591-596
    Cordes T, Wallace M, Michelucci A, Divakaruni AS, Sapcariu SC, Sousa C, Koseki H, Cabrales P, Murphy AN, Hiller K et al (2016) Immunoresponsive gene 1 and itaconate inhibit succinate dehydrogenase to modulate intracellular succinate levels. J Biol Chem 291:14274-14284
    Covarrubias AJ, Aksoylar HI, Yu JJ, Snyder NW, Worth AJ, Iyer SS, Wang JW, Ben-Sahra I, Byles V, Polynne-Stapornkul T et al (2016) Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation. Elife 5
    Cravo ML, Pinto AG, Chaves P, Cruz JA, Lage P, Nobre Leitao C, Costa Mira F (1998) Effect of folate supplementation on DNA methylation of rectal mucosa in patients with colonic adenomas:correlation with nutrient intake. Clin Nutr 17:45-49
    Crider KS, Yang TP, Berry RJ, Bailey LB (2012) Folate and DNA methylation:a review of molecular mechanisms and the evidence for folate's role. Adv Nutr 3:21-38
    Dai ZW, Mentch SJ, Gao X, Nichenametla SN, Locasale JW (2018) Methionine metabolism influences genomic architecture and gene expression through H3K4me3 peak width. Nat Commun 9
    Dai ZW, Ramesh V, Locasale JW (2020) The evolving metabolic landscape of chromatin biology and epigenetics. Nat Rev Genet 21:737-753
    Daigle SR, Olhava EJ, Therkelsen CA, Majer CR, Sneeringer CJ, Song J, Johnston LD, Scott MP, Smith JJ, Xiao YH et al (2011) Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell 20:53-65
    Daigle SR, Olhava EJ, Therkelsen CA, Basavapathruni A, Jin L, Boriack-Sjodin PA, Allain CJ, Klaus CR, Raimondi A, Scott MP et al (2013) Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood 122:1017-1025
    Dang CV (2012) MYC on the path to cancer. Cell 149:22-35
    Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739-U752
    Daniels BP, Kofman SB, Smith JR, Norris GT, Snyder AG, Kolb JP, Gao X, Locasale JW, Martinez J, Gale M et al (2019) The nucleotide sensor ZBP1 and kinase RIPK3 induce the enzyme IRG1 to promote an antiviral metabolic state in neurons. Immunity 50:64-76
    Darrah E, Andrade F (2018) Rheumatoid arthritis and citrullination. Curr Opin Rheumatol 30:72-78
    Datta J, Ghoshal K, Denny WA, Gamage SA, Brooke DG, Phiasivongsa P, Redkar S, Jacob ST (2009) A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation. Cancer Res 69:4277-4285
    Daw CC, Ramachandran K, Enslow BT, Maity S, Bursic B, Novello MJ, Rubannelsonkumar CS, Mashal AH, Ravichandran J, Bakewell TM et al (2020) Lactate elicits ER-mitochondrial Mg(2+) dynamics to integrate cellular metabolism. Cell.
    Dawson MA, Bannister AJ, Gottgens B, Foster SD, Bartke T, Green AR, Kouzarides T (2009) JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature 461:819-822
    Dawson MA, Prinjha RK, Dittmann A, Giotopoulos G, Bantscheff M, Chan WI, Robson SC, Chung CW, Hopf C, Savitski MM et al (2011) Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 478:529-533
    de Boer VC, Houten SM (2014) A mitochondrial expatriate:nuclear pyruvate dehydrogenase. Cell 158:9-10
    De Ruijter AJM, Van Gennip AH, Caron HN, Kemp S, Van Kuilenburg ABP (2003) Histone deacetylases (HDACs):characterization of the classical HDAC family. Biochem J 370:737-749
    De Virgilio C, Burckert N, Barth G, Neuhaus JM, Boller T, Wiemken A (1992) Cloning and disruption of a gene required for growth on acetate but not on ethanol:the acetyl-coenzyme A synthetase gene of Saccharomyces cerevisiae. Yeast 8:1043-1051
    DeBerardinis RJ, Chandel NS (2016) Fundamentals of cancer metabolism. Sci Adv 2
    DeBerardinis RJ, Thompson CB (2012) Cellular Metabolism and Disease:What Do Metabolic Outliers Teach Us? Cell 148:1132-1144
    DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB (2008a) The biology of cancer:Metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7:11-20
    DeBerardinis RJ, Sayed N, Ditsworth D, Thompson CB (2008b) Brick by brick:metabolism and tumor cell growth. Curr Opin Genet Dev 18:54-61
    Dehennaut V, Leprince D, Lefebvre T (2014) O-GlcNAcylation, an epigenetic mark. Focus on the histone code, TET family proteins, and polycomb group proteins. Front Endocrinol (Lausanne) 5:155
    Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi JW, Jacobs HM, Kastritis E, Gilpatrick T, Paranal RM, Qi J et al (2011) BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 146:903-916
    Demers, M., Wong, S.L., Martinod, K., Gallant, M., Cabral, J.E., Wang, Y.M., and Wagner, D.D. (2016). Priming of neutrophils toward NETosis promotes tumor growth. Oncoimmunology 5.
    Denny WA, Atwell GJ, Baguley BC, Cain BF (1979) Potential antitumor agents. 29. Quantitative structure-activity relationships for the antileukemic bisquaternary ammonium heterocycles. J Med Chem 22:134-150
    Dentin R, Hedrick S, Xie JX, Yates J, Montminy M (2008) Hepatic glucose sensing via the CREB coactivator CRTC2. Science 319:1402-1405
    Deplus R, Delatte B, Schwinn MK, Defrance M, Mendez J, Murphy N, Dawson MA, Volkmar M, Putmans P, Calonne E et al (2013) TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J 32:645-655
    Di Lorenzo A, Bedford MT (2011) Histone arginine methylation. FEBS Lett 585:2024-2031
    Dimitrova E, Turberfield AH, Klose RJ (2015) Histone demethylases in chromatin biology and beyond. EMBO Rep 16:1620-1639
    Ding W, Smulan LJ, Hou NS, Taubert S, Watts JL, Walker AK (2015) s-Adenosylmethionine levels govern innate immunity through distinct methylation-dependent pathways. Cell Metab 22:633-645
    Dominguez-Andres J, Novakovic B, Li Y, Scicluna BP, Gresnigt MS, Arts RJW, Oosting M, Moorlag SJCFM, Groh LA, Zwaag J et al (2019) The itaconate pathway is a central regulatory node linking innate immune tolerance and trained immunity. Cell Metab 29:211-220
    Donohoe DR, Collins LB, Wali A, Bigler R, Sun W, Bultman SJ (2012) The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol Cell 48:612-626
    Du JT, Zhou YY, Su XY, Yu JJ, Khan S, Jiang H, Kim J, Woo J, Kim JH, Choi BH et al (2011) Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science 334:806-809
    Dunbar EM, Coats BS, Shroads AL, Langaee T, Lew A, Forder JR, Shuster JJ, Wagner DA, Stacpoole PW (2014) Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors. Invest New Drugs 32:452-464
    Eckschlager, T., Plch, J., Stiborova, M., and Hrabeta, J. (2017). Histone Deacetylase Inhibitors as Anticancer Drugs. International Journal of Molecular Sciences 18.
    Eden A, Gaudet F, Waghmare A, Jaenisch R (2003) Chromosomal instability and tumors promoted by DNA hypomethylation. Science 300:455
    Edmunds LR, Sharma L, Kang A, Lu J, Vockley J, Basu S, Uppala R, Goetzman ES, Beck ME, Scott D et al (2014) c-Myc programs fatty acid metabolism and dictates acetyl-CoA abundance and fate. J Biol Chem 289:25382-25392
    Eisenberg T, Schroeder S, Andryushkova A, Pendl T, Kuttner V, Bhukel A, Marino G, Pietrocola F, Harger A, Zimmermann A et al (2014) Nucleocytosolic depletion of the energy metabolite acetyl-coenzyme a stimulates autophagy and prolongs lifespan. Cell Metab 19:431-444
    Ellinger J, Kahl P, Mertens C, Rogenhofer S, Hauser S, Hartmann W, Bastian PJ, Buttner R, Muller SC, von Ruecker A (2010) Prognostic relevance of global histone H3 lysine 4 (H3K4) methylation in renal cell carcinoma. Int J Cancer 127:2360-2366
    Elsheikh SE, Green AR, Rakha EA, Powe DG, Ahmed RA, Collins HM, Soria D, Garibaldi JM, Paish CE, Ammar AA et al (2009) Global histone modifications in breast cancer correlate with tumor phenotypes, prognostic factors, and patient outcome. Cancer Res 69:3802-3809
    Esteller M, Avizienyte E, Corn PG, Lothe RA, Baylin SB, Aaltonen LA, Herman JG (2000) Epigenetic inactivation of LKB1 in primary tumors associated with the Peutz-Jeghers syndrome. Oncogene 19:164-168
    Esteller M, Corn PG, Baylin SB, Herman JG (2001) A gene hypermethylation profile of human cancer. Cancer Res 61:3225-3229
    Etchegaray JP, Mostoslavsky R (2016) Interplay between metabolism and epigenetics:a nuclear adaptation to environmental changes. Mol Cell 62:695-711
    Evans JS, Mengel GD (1964) The reversal of cytosine arabinoside activity in vivo by deoxycytidine. Biochem Pharmacol 13:989-994
    Faiola F, Liu X, Lo S, Pan S, Zhang K, Lymar E, Farina A, Martinez E (2005) Dual regulation of c-Myc by p300 via acetylation-dependent control of Myc protein turnover and coactivation of Myc-induced transcription. Mol Cell Biol 25:10220-10234
    Falkenberg KJ, Johnstone RW (2014) Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discovery 13:673-691
    Fan J, Teng X, Liu L, Mattaini KR, Looper RE, Vander Heiden MG, Rabinowitz JD (2015) Human phosphoglycerate dehydrogenase produces the oncometabolite D-2-hydroxyglutarate. ACS Chem Biol 10:510-516
    Faubert B, Li KY, Cai L, Hensley CT, Kim J, Zacharias LG, Yang C, Do QN, Doucette S, Burguete D et al (2017) Lactate metabolism in human lung tumors. Cell 171(358-371):
    Faubert, B., Solmonson, A., and DeBerardinis, R.J. (2020). Metabolic reprogramming and cancer progression. Science 368.
    Feinberg AP, Tycko B (2004) Timeline-The history of cancer epigenetics. Nat Rev Cancer 4:143-153
    Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301:89-92
    Feldman JL, Baeza J, Denu JM (2013) Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins. J Biol Chem 288:31350-31356
    Feng Q, Wang HB, Ng HH, Erdjument-Bromage H, Tempst P, Struhl K, Zhang Y (2002) Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain. Curr Biol 12:1052-1058
    Ferrer CM, Lynch TP, Sodi VL, Falcone JN, Schwab LP, Peacock DL, Vocadlo DJ, Seagroves TN, Reginato MJ (2014) O-GlcNAcylation regulates cancer metabolism and survival stress signaling via regulation of the HIF-1 pathway. Mol Cell 54:820-831
    Ferrer CM, Sodi VL, Reginato MJ (2016) O-GlcNAcylation in cancer biology:linking metabolism and signaling. J Mol Biol 428:3282-3294
    Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, Li YS, Bhagwat N, Vasanthakumar A, Fernandez HF et al (2010) Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 18:553-567
    Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I et al (2010) Selective inhibition of BET bromodomains. Nature 468:1067-1073
    Filippov S, Pinkosky SL, Newton RS (2014) LDL-cholesterol reduction in patients with hypercholesterolemia by modulation of adenosine triphosphate-citrate lyase and adenosine monophosphate-activated protein kinase. Curr Opin Lipidol 25:309-315
    Fleming SE, Fitch MD, DeVries S, Liu ML, Kight C (1991) Nutrient utilization by cells isolated from rat jejunum, cecum and colon. J Nutr 121:869-878
    Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G, Bonaldi T, Haydon C, Ropero S, Petrie K et al (2005) Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet 37:391-400
    Fuhrmann J, Thompson PR (2016) Protein arginine methylation and citrullination in epigenetic regulation. ACS Chem Biol 11:654-668
    Fujino T, Kondo J, Ishikawa M, Morikawa K, Yamamoto TT (2001) Acetyl-CoA synthetase 2, a mitochondrial matrix enzyme involved in the oxidation of acetate. J Biol Chem 276:11420-11426
    Fujisawa T, Filippakopoulos P (2017) Functions of bromodomain-containing proteins and their roles in homeostasis and cancer. Nat Rev Mol Cell Biol 18:246-262
    Galeotti F, Barile E, Curir P, Dolci M, Lanzotti V (2008) Flavonoids from carnation (Dianthus caryophyllus) and their antifungal activity. Phytochem Lett 1:44-48
    Gambetta MC, Oktaba K, Muller J (2009) Essential role of the glycosyltransferase sxc/Ogt in polycomb repression. Science 325:93-96
    Gao, P., Tchernyshyov, I., Chang, T.C., Lee, Y.S., Kita, K., Ochi, T., Zeller, K., De Marzo, A., Van Eyk, J., Mendell, J., et al. (2009). c-Myc suppression of miR-23 enhances mitochondrial glutaminase and glutamine metabolism. Cancer Research 69.
    Gao, X., Lin, S.H., Ren, F., Li, J.T., Chen, J.J., Yao, C.B., Yang, H.B., Jiang, S.X., Yan, G.Q., Wang, D., et al. (2016). Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia. Nature Communications 7.
    Garcia JM, Silva J, Pena C, Garcia V, Rodriguez R, Cruz MA, Cantos B, Provencio M, Espana P, Bonilla F (2004) Promoter methylation of the PTEN gene is a common molecular change in breast cancer. Genes Chromosom Cancer 41:117-124
    Garcia BA, Luka Z, Loukachevitch LV, Bhanu NV, Wagner C (2016) Folate deficiency affects histone methylation. Med Hypotheses 88:63-67
    Gates LA, Shi JJ, Rohira AD, Feng Q, Zhu BK, Bedford MT, Sagum CA, Jung SY, Qin J, Tsai MJ et al (2017) Acetylation on histone H3 lysine 9 mediates a switch from transcription initiation to elongation. J Biol Chem 292:14456-14472
    Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J, Gray JW, Leonhardt H, Jaenisch R (2003) Induction of tumors in mice by genomic hypomethylation. Science 300:489-492
    Giet R, Glover DM (2001) Drosophila Aurora B kinase is required for histone H3 phosphorylation and condensin recruitment during chromosome condensation and to organize the central spindle during cytokinesis. J Cell Biol 152:669-681
    Goffin J, Eisenhauer E (2002) DNA methyltransferase inhibitors-state of the art. Ann Oncol 13:1699-1716
    Golks A, Tran TT, Goetschy JF, Guerini D (2007) Requirement for O-linked N-acetylglucosaminyltransferase in lymphocytes activation. EMBO J 26:4368-4379
    Goncalves MD, Lu CY, Tutnauer J, Hartman TE, Hwang SK, Murphy CJ, Pauli C, Morris R, Taylor S, Bosch K et al (2019) High-fructose corn syrup enhances intestinal tumor growth in mice. Science 363:1345-1349
    Gongol, B., Sari, I., Bryant, T., Rosete, G., and Marin, T. (2018). AMPK:An Epigenetic Landscape Modulator. International Journal of Molecular Sciences 19.
    Goudarzi A, Zhang D, Huang H, Barral S, Kwon OK, Qi S, Tang Z, Buchou T, Vitte AL, He T et al (2016) Dynamic competing histone H4 K5K8 acetylation and butyrylation are hallmarks of highly active gene promoters. Mol Cell 62:169-180
    Gounaris AD, Perlmann GE (1967) Succinylation of pepsinogen. J Biol Chem 242:2739-2745
    Gravel SP, Hulea L, Toban N, Birman E, Blouin MJ, Zakikhani M, Zhao YH, Topisirovic I, St-Pierre J, Pollak M (2014) Serine deprivation enhances antineoplastic activity of biguanides. Cancer Res 74:7521-7533
    Greenberg MVC, Bourc'his D (2019) The diverse roles of DNA methylation in mammalian development and disease. Nat Rev Mol Cell Biol 20:590-607
    Greene KS, Lukey MJ, Wang XY, Blank B, Druso JE, Lin MCJ, Stalnecker CA, Zhang CL, Abril YN, Erickson JW et al (2019) SIRT5 stabilizes mitochondrial glutaminase and supports breast cancer tumorigenesis. Proc Natl Acad Sci USA 116:26625-26632
    Greer EL, Shi Y (2012) Histone methylation:a dynamic mark in health, disease and inheritance. Nat Rev Genet 13:343-357
    Gross S, Cairns RA, Minden MD, Driggers EM, Bittinger MA, Jang HG, Sasaki M, Jin SF, Schenkein DP, Su SSM et al (2010) Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med 207:339-344
    Gu YC, Mi WY, Ge YQ, Liu HY, Fan QO, Han CF, Yang J, Han F, Lu XZ, Yu WG (2010) GlcNAcylation plays an essential role in breast cancer metastasis. Cancer Res 70:6344-6351
    Guccione E, Richard S (2019) The regulation, functions and clinical relevance of arginine methylation. Nat Rev Mol Cell Biol 20:642-657
    Guo H, Tan Y, Kubota T, Moossa AR, Hoffman RM (1996) Methionine depletion modulates the antitumor and antimetastatic efficacy of ethionine. Anticancer Res 16:2719-2723
    Gutierrez RM, Hnilica LS (1967) Tissue specificity of histone phosphorylation. Science 157:1324-1325
    Gutierrez MJ, Rosenberg NL, MacDougall DE, Hanselman JC, Margulies JR, Strange P, Milad MA, McBride SJ, Newton RS (2014) Efficacy and Safety of ETC-1002, a novel investigational low-density lipoprotein-cholesterol-lowering therapy for the treatment of patients with hypercholesterolemia and Type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol 34:676-683
    Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ (2008) Review article:the role of butyrate on colonic function. Aliment Pharmacol Ther 27:104-119
    Hanahan D, Weinberg RA (2011) Hallmarks of cancer:the next generation. Cell 144:646-674
    Hannou SA, Haslam DE, McKeown NM, Herman MA (2018) Fructose metabolism and metabolic disease. J Clin Invest 128:545-555
    Hao HX, Khalimonchuk O, Schraders M, Dephoure N, Bayley JP, Kunst H, Devilee P, Cremers CWRJ, Schiffman JD, Bentz BG et al (2009) SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science 325:1139-1142
    Hardie DG (2011) AMP-activated protein kinase-an energy sensor that regulates all aspects of cell function. Genes Dev 25:1895-1908
    Hardie DG, Schaffer BE, Brunet A (2016) AMPK:an energy-sensing pathway with multiple inputs and outputs. Trends Cell Biol 26:190-201
    Hardiville S, Hart GW (2014) Nutrient regulation of signaling, transcription, and cell physiology by O-GlcNAcylation. Cell Metab 20:208-213
    Harris RA, Joshi M, Jeoung NH, Obayashi M (2005) Overview of the molecular and biochemical basis of branched-chain amino acid catabolism. J Nutr 135:1527s-1530s
    Hart GW (2019) Nutrient regulation of signaling and transcription. J Biol Chem 294:2211-2231
    Hart GW, Housley MP, Slawson C (2007) Cycling of O-linked beta-N-acetylglucosamine on nucleocytoplasmic proteins. Nature 446:1017-1022
    Hart GW, Slawson C, Ramirez-Correa G, Lagerlof O (2011) Cross talk between O-GlcNAcylation and phosphorylation:roles in signaling, transcription, and chronic disease. Annu Rev Biochem 80(80):825-858
    Harutyunyan AS, Krug B, Chen HF, Papillon-Cavanagh S, Zeinieh M, De Jay N, Deshmukh S, Chen CCL, Belle J, Mikael LG et al (2019) H3K27M induces defective chromatin spread of PRC2-mediated repressive H3K27me2/me3 and is essential for glioma tumorigenesis. Nat Commun 10
    Hatzivassiliou G, Zhao FP, Bauer DE, Andreadis C, Shaw AN, Dhanak D, Hingorani SR, Tuveson DA, Thompson CB (2005) ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 8:311-321
    Haws SA, Leech CM, Denu JM (2020) Metabolism and the epigenome:a dynamic relationship. Trends Biochem Sci
    Hayakawa K, Hirosawa M, Tabei Y, Arai D, Tanaka S, Murakami N, Yagi S, Shiota K (2013) Epigenetic switching by the metabolism-sensing factors in the generation of orexin neurons from mouse embryonic stem cells. J Biol Chem 288:17099-17110
    Heiden MGV, Cantley LC, Thompson CB (2009) Understanding the warburg effect:the metabolic requirements of cell proliferation. Science 324:1029-1033
    Herman JG, Latif F, Weng Y, Lerman MI, Zbar B, Liu S, Samid D, Duan DS, Gnarra JR, Linehan WM et al (1994) Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci USA 91:9700-9704
    Herzig S, Raemy E, Montessuit S, Veuthey JL, Zamboni N, Westermann B, Kunji ER, Martinou JC (2012) Identification and functional expression of the mitochondrial pyruvate carrier. Science 337:93-96
    Hirschey MD, Zhao YM (2015) Metabolic regulation by lysine malonylation, succinylation, and glutarylation. Mol Cell Proteomics 14:2308-2315
    Hirschey MD, Shimazu T, Goetzman E, Jing E, Schwer B, Lombard DB, Grueter CA, Harris C, Biddinger S, Ilkayeva OR et al (2010) SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature 464:121-U137
    Hirschey MD, DeBerardinis RJ, Diehl AME, Drew JE, Frezza C, Green MF, Jones LW, Ko YH, Le A, Lea MA et al (2015) Dysregulated metabolism contributes to oncogenesis. Semin Cancer Biol 35:S129-S150
    Hitosugi T, Fan J, Chung TW, Lythgoe K, Wang X, Xie JX, Ge QY, Gu TL, Polakiewicz RD, Roesel JL et al (2011) Tyrosine phosphorylation of mitochondrial pyruvate dehydrogenase kinase 1 is important for cancer metabolism. Mol Cell 44:864-877
    Holleran JL, Parise RA, Joseph E, Eiseman JL, Covey JM, Glaze ER, Lyubimov AV, Chen YF, D'Argenio DZ, Egorin MJ (2005) Plasma pharmacokinetics, oral bioavailability, and interspecies scaling of the DNA methyltransferase inhibitor, zebularine. Clin Cancer Res 11:3862-3868
    Hooftman A, Angiari S, Hester S, Corcoran SE, Runtsch MC, Ling C, Ruzek MC, Slivka PF, McGettrick AF, Banahan K et al (2020) The immunomodulatory metabolite itaconate modifies NLRP3 and inhibits inflammasome activation. Cell Metab 32:468-478
    Hopkins BD, Pauli C, Du X, Wang DG, Li X, Wu D, Amadiume SC, Goncalves MD, Hodakoski C, Lundquist MR et al (2018) Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature 560:499-503
    Hoshiya Y, Kubota T, Inada T, Kitajima M, Hoffman RM (1997) Methionine-depletion modulates the efficacy of 5-fluorouracil in human gastric cancer in nude mice. Anticancer Res 17:4371-4375
    Housley MP, Rodgers JT, Udeshi ND, Kelly TJ, Shabanowitz J, Hunt DF, Puigserver P, Hart GW (2008) O-GlcNAc regulates FoxO activation in response to glucose. J Biol Chem 283:16283-16292
    Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL et al (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425:191-196
    Hsu PC, Liao YF, Lin CL, Lin WH, Liu GY, Hung HC (2014) Vimentin is involved in peptidylarginine deiminase 2-induced apoptosis of activated jurkat cells. Mol Cells 37:426-434
    Hubbard BP, Gomes AP, Dai H, Li J, Case AW, Considine T, Riera TV, Lee JE, Yen ES, Lamming DW et al (2013) Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science 339:1216-1219
    Hughey CC, Trefts E, Bracy DP, James FD, Donahue EP, Wasserman DH (2018) Glycine N-methyltransferase deletion in mice diverts carbon flux from gluconeogenesis to pathways that utilize excess methionine cycle intermediates. J Biol Chem 293:11944-11954
    Hui S, Ghergurovich JM, Morscher RJ, Jang C, Teng X, Lu W, Esparza LA, Reya T, Le Z, Yanxiang Guo J et al (2017) Glucose feeds the TCA cycle via circulating lactate. Nature 551:115-118
    Hwang IY, Kwak S, Lee S, Kim H, Lee SE, Kim JH, Kim YA, Jeon YK, Chung DH, Jin X et al (2016) Psat1-Dependent fluctuations in alpha-ketoglutarate affect the timing of ESC differentiation. Cell Metab 24:494-501
    Hyun K, Jeon J, Park K, Kim J (2017) Writing, erasing and reading histone lysine methylations. Exp Mol Med 49
    Icard P, Poulain L, Lincet H (2012) Understanding the central role of citrate in the metabolism of cancer cells. Biochim Biophys Acta 1825:111-116
    Icard P, Wu ZR, Fournel L, Coquerel A, Lincet H, Alifano M (2020) ATP citrate lyase:A central metabolic enzyme in cancer. Cancer Lett 471:125-134
    Intlekofer AM, Dematteo RG, Venneti S, Finley LWS, Lu C, Judkins AR, Rustenburg AS, Grinaway PB, Chodera JD, Cross JR et al (2015) Hypoxia induces production of L-2-hydroxyglutarate. Cell Metab 22:304-311
    Ishak Gabra MB, Yang Y, Li H, Senapati P, Hanse EA, Lowman XH, Tran TQ, Zhang L, Doan LT, Xu X et al (2020) Dietary glutamine supplementation suppresses epigenetically-activated oncogenic pathways to inhibit melanoma tumour growth. Nat Commun 11:3326
    Ivashkiv LB (2013) Epigenetic regulation of macrophage polarization and function. Trends Immunol 34:216-223
    Jang MK, Mochizuki K, Zhou MS, Jeong HS, Brady JN, Ozato K (2005) The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription. Mol Cell 19:523-534
    Janke R, Dodson AE, Rine J (2015) Metabolism and epigenetics. Annu Rev Cell Dev Biol 31:473-496
    Jensen T, Abdelmalek MF, Sullivan S, Nadeau KJ, Green M, Roncal C, Nakagawa T, Kuwabara M, Sato Y, Kang DH et al (2018) Fructose and sugar:a major mediator of non-alcoholic fatty liver disease. J Hepatol 68:1063-1075
    Jeon H, Kim JH, Lee E, Jang YJ, Son JE, Kwon JY, Lim TG, Kim S, Park JH, Kim JE et al (2016) Methionine deprivation suppresses triple-negative breast cancer metastasis in vitro and in vivo. Oncotarget 7:67223-67234
    Jha AK, Huang SCC, Sergushichev A, Lampropoulou V, Ivanova Y, Loginicheva E, Chmielewski K, Stewart KM, Ashall J, Everts B et al (2015) Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 42:419-430
    Jiang WQ, Wang SW, Xiao MT, Lin Y, Zhou LS, Lei QY, Xiong Y, Guan KL, Zhao SM (2011) Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase. Mol Cell 43:33-44
    Jing H, Lin HN (2015) Sirtuins in epigenetic regulation. Chem Rev 115:2350-2375
    Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3:415-428
    Jones RG, Thompson CB (2009) Tumor suppressors and cell metabolism:a recipe for cancer growth. Genes Dev 23:537-548
    Kaczmarska Z, Ortega E, Goudarzi A, Huang H, Kim S, Marquez JA, Zhao YM, Khochbin S, Panne D (2017) Structure of p300 in complex with acyl-CoA variants. Nat Chem Biol 13:21-29
    Kaelin WG (2009) SDH5 Mutations and Familial Paraganglioma:Somewhere Warburg is Smiling. Cancer Cell 16:180-182
    Kaelin WG, McKnight SL (2013) Influence of Metabolism on Epigenetics and Disease. Cell 153:56-69
    Kaminskas E, Farrell A, Abraham S, Baird A, Hsieh LS, Lee SL, Leighton JK, Patel H, Rahman A, Sridhara R et al (2005a) Approval summary:Azacitidine for treatment of myelodysplastic syndrome subtypes. Clin Cancer Res 11:3604-3608
    Kaminskas E, Farrell AT, Wang YC, Sridhara R, Pazdur R (2005b) FDA drug approval summary:Azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist 10:176-182
    Kang YH, Lee HS, Kim WH (2002) Promoter methylation and silencing of PTEN in gastric carcinoma. Lab Invest 82:285-291
    Kaplon J, Zheng L, Meissl K, Chaneton B, Selivanov VA, Mackay G, van der Burg SH, Verdegaal EM, Cascante M, Shlomi T et al (2013) A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence. Nature 498:109-112
    Karahoca M, Momparler RL (2013) Pharmacokinetic and pharmacodynamic analysis of 5-aza-2'-deoxycytidine (decitabine) in the design of its dose-schedule for cancer therapy. Clin Epigenetics 5:3
    Katoh Y, Ikura T, Hoshikawa Y, Tashiro S, Ito T, Ohta M, Kera Y, Noda T, Igarashi K (2011) Methionine adenosyltransferase II serves as a transcriptional corepressor of maf oncoprotein. Mol Cell 41:554-566
    Katsyuba E, Mottis A, Zietak M, De Franco F, van der Velpen V, Gariani K, Ryu D, Cialabrini L, Matilainen O, Liscio P et al (2018) De novo NAD(+) synthesis enhances mitochondrial function and improves health. Nature 563:354-359
    Keating ST, El-Osta A (2015) Epigenetics and metabolism. Circ Res 116:715-736
    Kelly B, Pearce EL (2020). Amino assets:how amino acids support immunity. Cell Metab
    Kelly WG, Dahmus ME, Hart GW (1993) RNA polymerase II is a glycoprotein. Modification of the COOH-terminal domain by O-GlcNAc. J Biol Chem 268:10416-10424
    Kera Y, Katoh Y, Ohta M, Matsumoto M, Takano-Yamamoto T, Igarashi K (2013) Methionine adenosyltransferase II-dependent histone H3K9 methylation at the COX-2 gene locus. J Biol Chem 288:13592-13601
    Kidwai SA, Ansari AA, Salahuddin A (1976) Effect of succinylation (3-carboxypropionylation) on the conformation and immunological activity of ovalbumin. Biochem J 155:171-180
    Kim JW, Tchernyshyov I, Semenza GL, Dang CV (2006) HIF-1-mediated expression of pyruvate dehydrogenase kinase:a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 3:177-185
    Kim SR, Kim KB, Chae YC, Park JW, Seo SB (2016) H3S10 phosphorylation-mediated transcriptional regulation by Aurora kinase A. Biochem Biophys Res Commun 469:22-28
    Kinnaird A, Zhao S, Wellen KE, Michelakis ED (2016) Metabolic control of epigenetics in cancer. Nat Rev Cancer 16:694-707
    Kleinsmith LJ, Allfrey VG, Mirsky AE (1966) Phosphoprotein metabolism in isolated lymphocyte nuclei. Proc Natl Acad Sci USA 55:1182-1189
    Klement RJ (2019) The emerging role of ketogenic diets in cancer treatment. Curr Opin Clin Nutr Metab Care 22:129-134
    Knight JS, Subramanian V, O'Dell AA, Yalavarthi S, Zhao WP, Smith CK, Hodgin JB, Thompson PR, Kaplan MJ (2015) Peptidylarginine deiminase inhibition disrupts NET formation and protects against kidney, skin and vascular disease in lupus-prone MRL/lpr mice. Ann Rheum Dis 74:2199-2206
    Knutson SK, Wigle TJ, Warholic NM, Sneeringer CJ, Allain CJ, Klaus CR, Sacks JD, Raimondi A, Majer CR, Song J et al (2012) A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol 8:890-896
    Knutson SK, Kawano S, Minoshima Y, Warholic NM, Huang KC, Xiao YH, Kadowaki T, Uesugi M, Kuznetsov G, Kumar N et al (2014) Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-hodgkin lymphoma. Mol Cancer Ther 13:842-854
    Koenis DS, Medzikovic L, van Loenen PB, van Weeghel M, Huveneers S, Vos M, Evers-van Gogh IJ, Van den Bossche J, Speijer D, Kim Y et al (2018) Nuclear receptor nur77 limits the macrophage inflammatory response through transcriptional reprogramming of mitochondrial metabolism. Cell Reports 24:2127-2140
    Koivunen P, Lee S, Duncan CG, Lopez G, Lu G, Ramkissoon S, Losman JA, Joensuu P, Bergmann U, Gross S et al (2012) Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation. Nature 483:485
    Konig MF, Abusleme L, Reinholdt J, Palmer RJ, Teles RP, Sampson K, Rosen A, Nigrovic PA, Sokolove J, Giles JT et al (2016) Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. Sci Transl Med 8
    Kottakis F, Nicolay BN, Roumane A, Karnik R, Gu HC, Nagle JM, Boukhali M, Hayward MC, Li YY, Chen T et al (2016) LKB1 loss links serine metabolism to DNA methylation and tumorigenesis. Nature 539:390-395
    Kryukov GV, Wilson FH, Ruth JR, Paulk J, Tsherniak A, Marlow SE, Vazquez F, Weir BA, Fitzgerald ME, Tanaka M et al (2016) MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells. Science 351:1214-1218
    Kumari R, Deshmukh RS, Das S (2019) Caspase-10 inhibits ATP-citrate lyase-mediated metabolic and epigenetic reprogramming to suppress tumorigenesis. Nat Commun 10
    Kurmi K, Hitosugi S, Wiese EK, Boakye-Agyeman F, Gonsalves WI, Lou ZK, Karnitz LM, Goetz MP, Hitosugi T (2018) Carnitine palmitoyltransferase 1A Has a lysine succinyltransferase activity. Cell Rep 22:1365-1373
    Lacoste N, Utley RT, Hunter JM, Poirier GG, Cote J (2002) Disruptor of telomeric silencing-1 is a chromatin-specific histone H3 methyltransferase. J Biol Chem 277:30421-30424
    Lampropoulou V, Sergushichev A, Bambouskova M, Nair S, Vincent EE, Loginicheva E, Cervantes-Barragan L, Ma XC, Huang SCC, Griss T et al (2016) Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation. Cell Metab 24:158-166
    Langan TA (1968) Histone phosphorylation:stimulation by adenosine 3',5'-monophosphate. Science 162:579-580
    Laribee RN (2018) Transcriptional and epigenetic regulation by the mechanistic target of rapamycin complex 1 pathway. J Mol Biol 430:4874-4890
    Latham T, Mackay L, Sproul D, Karim M, Culley J, Harrison DJ, Hayward L, Langridge-Smith P, Gilbert N, Ramsahoye BH (2012) Lactate, a product of glycolytic metabolism, inhibits histone deacetylase activity and promotes changes in gene expression. Nucleic Acids Res 40:4794-4803
    Lauterbach MA, Hanke JE, Serefidou M, Mangan MSJ, Kolbe CC, Hess T, Rothe M, Kaiser R, Hoss F, Gehlen J et al (2019) Toll-like receptor signaling rewires macrophage metabolism and promotes histone acetylation via ATP-citrate lyase. Immunity 51(997-1011):
    Lavu S, Boss O, Elliott PJ, Lambert PD (2008) Sirtuins-novel therapeutic targets to treat age-associated diseases. Nat Rev Drug Discovery 7:841-853
    Lee CG, Jenkins NA, Gilbert DJ, Copeland NG, O'Brien WE (1995) Cloning and analysis of gene regulation of a novel LPS-inducible cDNA. Immunogenetics 41:263-270
    Lee JV, Carrer A, Shah S, Snyder NW, Wei SZ, Venneti S, Worth AJ, Yuan ZF, Lim HW, Liu SC et al (2014) Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation. Cell Metab 20:306-319
    Lee CF, Caudal A, Abell L, Gowda GAN, Tian R (2019) Targeting NAD(+) metabolism as interventions for mitochondrial disease. Sci Rep 9
    Lei MZ, Li XX, Zhang Y, Li JT, Zhang F, Wang YP, Yin M, Qu J, Lei QY (2020) Acetylation promotes BCAT2 degradation to suppress BCAA catabolism and pancreatic cancer growth. Signal Transduct Target Ther 5:70
    Levine SS, King IF, Kingston RE (2004) Division of labor in polycomb group repression. Trends Biochem Sci 29:478-485
    Lewis BA, Hanover JA (2014) O-GlcNAc and the epigenetic regulation of gene expression. J Biol Chem 289:34440-34448
    Lewis PW, Muller MM, Koletsky MS, Cordero F, Lin S, Banaszynski LA, Garcia BA, Muir TW, Becher OJ, Allis CD (2013) Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma. Science 340:857-861
    Li JJ, Wang HX, Tino JA, Robl JA, Herpin TF, Lawrence RM, Biller S, Jamil H, Ponticiello R, Chen LP et al (2007) 2-Hydroxy-N-arylbenzenesulfonamides as ATP-citrate lyase inhibitors. Bioorg Med Chem Lett 17:3208-3211
    Li PX, Yao HJ, Zhang ZQ, Li M, Luo Y, Thompson PR, Gilmour DS, Wang YM (2008) Regulation of p53 target gene expression by peptidylarginine deiminase 4. Mol Cell Biol 28:4745-4758
    Li PX, Li M, Lindberg MR, Kennett MJ, Xiong N, Wang YM (2010) PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med 207:1853-1862
    Li MD, Ruan HB, Hughes ME, Lee JS, Singh JP, Jones SP, Nitabach MN, Yang XY (2013) O-GlcNAc signaling entrains the circadian clock by inhibiting BMAL1/CLOCK ubiquitination. Cell Metab 17:303-310
    Li TT, Liu MX, Feng X, Wang Z, Das I, Xu YP, Zhou X, Sun YP, Guan KL, Xiong Y et al (2014) Glyceraldehyde-3-phosphate dehydrogenase is activated by lysine 254 acetylation in response to glucose signal. J Biol Chem 289:3775-3785
    Li F, He XD, Ye DW, Lin Y, Yu HX, Yao CF, Huang L, Zhang JN, Wang F, Xu S et al (2015a) NADP(+)-IDH mutations promote hypersuccinylation that impairs mitochondria respiration and induces apoptosis resistance. Mol Cell 60:661-675
    Li SS, Swanson SK, Gogol M, Florens L, Washburn MP, Workman JL, Suganuma T (2015b) Serine and SAM responsive complex sesame regulates histone modification crosstalk by sensing cellular metabolism. Mol Cell 60:408-421
    Li L, Shi L, Yang SD, Yan RR, Zhang D, Yang JG, He L, Li WJ, Yi X, Sun LY et al (2016) SIRT7 is a histone desuccinylase that functionally links to chromatin compaction and genome stability. Nat Commun 7
    Li XJ, Qian X, Lu ZM (2017a) Local histone acetylation by ACSS2 promotes gene transcription for lysosomal biogenesis and autophagy. Autophagy 13:1790-1791
    Li XJ, Yu WL, Qian X, Xia Y, Zheng YH, Lee JH, Li W, Lyu JX, Rao G, Zhang XC et al (2017b) Nucleus-translocated ACSS2 promotes gene transcription for lysosomal biogenesis and autophagy. Mol Cell 66:684-697
    Li ST, Huang, Shen S, Cai Y, Xing S, Wu G, Jiang Z, Hao Y, Yuan M, Wang N et al (2020) Myc-mediated SDHA acetylation triggers epigenetic regulation of gene expression and tumorigenesis. Nat Metab 2:256-269
    Liao YJ, Liu SP, Lee CM, Yen CH, Chuang PC, Chen CY, Tsai TF, Huang SF, Lee YH, Chen YM (2009) Characterization of a glycine N-methyltransferase gene knockout mouse model for hepatocellular carcinoma:implications of the gender disparity in liver cancer susceptibility. Int J Cancer 124:816-826
    Lim JH, Lee YM, Chun YS, Chen J, Kim JE, Park JW (2010) Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1 alpha. Mol Cell 38:864-878
    Lin RT, Tao R, Gao X, Li TT, Zhou X, Guan KL, Xiong Y, Lei QY (2013) Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell 51:506-518
    Lin AP, Abbas S, Kim SW, Ortega M, Bouamar H, Escobedo Y, Varadarajan P, Qin Y, Sudderth J, Schulz E et al (2015) D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2. Nat Commun 6:7768
    Linder SJ, Mostoslavsky R (2017) Put your mark where your damage is:Acetyl-CoA production by ACLY promotes DNA repair. Mol Cell 67:165-167
    Liskiewicz AD, Kasprowska D, Wojakowska A, Polanski K, Lewin-Kowalik J, Kotulska K, Jedrzejowska-Szypulka H (2016) Long-term high fat ketogenic diet promotes renal tumor growth in a rat model of tuberous sclerosis. Sci Rep 6:21807
    Liu ZF, Xie ZL, Jones W, Pavlovicz RE, Liu SJ, Yu JH, Li PK, Lin JY, Fuchs JR, Marcucci G et al (2009) Curcumin is a potent DNA hypomethylation agent. Bioorg Med Chem Lett 19:706-709
    Liu Y, Liu K, Qin S, Xu C, Min J (2014) Epigenetic targets and drug discovery:part 1:histone methylation. Pharmacol Ther 143:275-294
    Liu K, Liu Y, Lau JL, Min J (2015) Epigenetic targets and drug discovery Part 2:histone demethylation and DNA methylation. Pharmacol Ther 151:121-140
    Liu PS, Wang HP, Li XY, Chao T, Christen TTS, Christen S, Di Conza G, Cheng WC, Chou CH, Vavakova M et al (2017) Alpha-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat Immunol 18:985-994
    Liu K, Li FZ, Sun QQ, Lin N, Han HC, You KQ, Tian F, Mao ZB, Li TT, Tong TJ et al (2019) p53 beta-hydroxybutyrylation attenuates p53 activity. Cell Death Dis 10
    Lo WS, Duggan L, Emre NCT, Belotserkovskya R, Lane WS, Shiekhattar R, Berger SL (2001) Snf1-a histone kinase that works in concert with the histone acetyltransferase Gcn5 to regulate transcription. Science 293:1142-1146
    Locasale JW (2013) Serine, glycine and one-carbon units:cancer metabolism in full circle. Nat Rev Cancer 13:572-583
    Losman JA, Kaelin WG (2013) What a difference a hydroxyl makes:mutant IDH, (R)-2-hydroxyglutarate, and cancer. Genes Dev 27:836-852
    Losman JA, Looper RE, Koivunen P, Lee S, Schneider RK, McMahon C, Cowley GS, Root DE, Ebert BL, Kaelin WG (2013) (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science 339:1621-1625
    Lozoya OA, Martinez-Reyes I, Wang T, Grenet D, Bushel P, Li J, Chandel N, Woychik RP, Santos JH (2018) Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation. PLoS Biol 16:
    Lu C, Ward PS, Kapoor GS, Rohle D, Turcan S, Abdel-Wahab O, Edwards CR, Khanin R, Figueroa ME, Melnick A et al (2012) IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 483:474
    Lu C, Venneti S, Akalin A, Fang F, Ward PS, DeMatteo RG, Intlekofer AM, Chen C, Ye JB, Hameed M et al (2013) Induction of sarcomas by mutant IDH2. Genes Dev 27:1986-1998
    Luan HH, Medzhitov R (2016) Food fight:role of itaconate and other metabolites in antimicrobial defense. Cell Metab 24:379-387
    Luka Z, Moss F, Loukachevitch LV, Bornhop DJ, Wagner C (2011) Histone demethylase LSD1 Is a folate-binding protein. Biochemistry 50:4750-4756
    Luka Z, Pakhomova S, Loukachevitch LV, Calcutt MW, Newcomer ME, Wagner C (2014) Crystal structure of the histone lysine specific demethylase LSD1 complexed with tetrahydrofolate. Protein Sci 23:993-998
    Luong A, Hannah VC, Brown MS, Goldstein JL (2000) Molecular characterization of human acetyl-CoA synthetase, an enzyme regulated by sterol regulatory element-binding proteins. J Biol Chem 275:26458-26466
    Lv L, Xu YP, Zhao D, Li FL, Wang W, Sasaki N, Jiang Y, Zhou X, Li TT, Guan KL et al (2013) Mitogenic and oncogenic stimulation of K433 acetylation promotes PKM2 protein kinase activity and nuclear localization. Mol Cell 52:340-352
    Ly A, Hoyt L, Crowell J, Kim YI (2012) Folate and DNA methylation. Antioxid Redox Signal 17:302-326
    Lyssiotis CA, Cantley LC (2014) Acetate fuels the cancer engine. Cell 159:1492-1494
    Ma RH, Ji TT, Zhang HF, Dong WQ, Chen XF, Xu PW, Chen DG, Liang XY, Yin XN, Liu YY et al (2018) A Pck1-directed glycogen metabolic program regulates formation and maintenance of memory CD8(+) T cells. Nat Cell Biol 20:21-27
    Maddocks ODK, Berkers CR, Mason SM, Zheng L, Blyth K, Gottlieb E, Vousden KH (2013) Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature 493:542-546
    Maddocks ODK, Labuschagne CF, Adams PD, Vousden KH (2016) Serine metabolism supports the Methionine cycle and DNA/RNA methylation through de novo ATP synthesis in cancer cells. Mol Cell 61:210-221
    Maddocks ODK, Athineos D, Cheung EC, Lee P, Zhang T, van den Broek NJF, Mackay GM, Labuschagne CF, Gay D, Kruiswijk F et al (2017) Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Nature 544:372-376
    Madeo F, Pietrocola F, Eisenberg T, Kroemer G (2014) Caloric restriction mimetics:towards a molecular definition. Nat Rev Drug Discovery 13:727-740
    Madsen AS, Andersen C, Daoud M, Anderson KA, Laursen JS, Chakladar S, Huynh FK, Colaco AR, Backos DS, Fristrup P et al (2016) Investigating the sensitivity of NAD+-dependent sirtuin deacylation activities to NADH. J Biol Chem 291:7128-7141
    Maher EA, Marin-Valencia I, Bachoo RM, Mashimo T, Raisanen J, Hatanpaa KJ, Jindal A, Jeffrey FM, Choi C, Madden C et al (2012) Metabolism of[U-13 C]glucose in human brain tumors in vivo. NMR Biomed 25:1234-1244
    Mahmood N, Rabbani SA (2019) DNA methylation readers and cancer:mechanistic and therapeutic applications. Front Oncol 9
    Maile T, Kwoczynski S, Katzenberger RJ, Wassarman DA, Sauer F (2004) TAF1 activates transcription by phosphorylation of serine 33 in histone H2B. Science 304:1010-1014
    Mann BS, Johnson JR, Cohen MH, Justice R, Pazdur R (2007) FDA approval summary:vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist 12:1247-1252
    Manuyakorn A, Paulus R, Farrell J, Dawson NA, Tze S, Cheung-Lau G, Hines OJ, Reber H, Seligson DB, Horvath S et al (2010) Cellular histone modification patterns predict prognosis and treatment response in resectable pancreatic adenocarcinoma:results from RTOG 9704. J Clin Oncol 28:1358-1365
    Marcucci G, Silverman L, Eller M, Lintz L, Beach CL (2005) Bioavailability of azacitidine subcutaneous versus intravenous in patients with the myelodysplastic syndromes. J Clin Pharmacol 45:597-602
    Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K, Koboldt DC, Fulton RS, Delehaunty KD, McGrath SD et al (2009) Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 361:1058-1066
    Marjon K, Cameron MJ, Quang P, Clasquin MF, Mandley E, Kunii K, Mcvay M, Choe S, Kernytsky A, Gross S et al (2016) MTAP deletions in cancer create vulnerability to targeting of the MAT2A/PRMT5/RIOK1 axis. Cell Rep 15:574-587
    Markham GD, Pajares MA (2009) Structure-function relationships in methionine adenosyltransferases. Cell Mol Life Sci 66:636-648
    Martinez Calejman C, Trefely S, Entwisle SW, Luciano A, Jung SM, Hsiao W, Torres A, Hung CM, Li H, Snyder NW et al (2020) mTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis. Nat Commun 11:575
    Martinez-Chantar ML, Vazquez-Chantada M, Ariz U, Martinez N, Varela M, Luka Z, Capdevila A, Rodriguez J, Aransay AM, Matthiesen R et al (2008) Loss of the glycine N-methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice. Hepatology 47:1191-1199
    Mashimo T, Pichumani K, Vemireddy V, Hatanpaa KJ, Singh DK, Sirasanagandla S, Nannepaga S, Piccirillo SG, Kovacs Z, Foong C et al (2014) Acetate is a bioenergetic substrate for human glioblastoma and brain metastases. Cell 159:1603-1614
    Tanikawa C, Espinosa M, Suzuki A, Masuda K, Yamamoto K, Tsuchiya E, Ueda K, Daigo Y, Nakamura Y, Matsuda, K (2012) Regulation of histone modification and chromatin structure by the p53-PADI4 pathway. Nat Commun 3
    Matsuda S, Adachi J, Ihara M, Tanuma N, Shima H, Kakizuka A, Ikura M, Ikura T, Matsuda T (2016) Nuclear pyruvate kinase M2 complex serves as a transcriptional coactivator of arylhydrocarbon receptor. Nucleic Acids Res 44:636-647
    Mattson MP, Chan SL (2003) Calcium orchestrates apoptosis. Nat Cell Biol 5:1041-1043
    Mauracher LM, Posch F, Martinod K, Grilz E, Daullary T, Hell L, Brostjan C, Zielinski C, Ay C, Wagner DD et al (2018) Citrullinated histone H3, a biomarker of neutrophil extracellular trap formation, predicts the risk of venous thromboembolism in cancer patients. J Thromb Haemost 16:508-518
    Mavrakis KJ, McDonald ER, Schlabach MR, Billy E, Hoffman GR, deWeck A, Ruddy DA, Venkatesan K, Yu JJ, McAllister G et al (2016) Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5. Science 351:1208-1213
    Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK (2009) Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal 2:ra46
    McBrian MA, Behbahan IS, Ferrari R, Su T, Huang TW, Li K, Hong CS, Christofk HR, Vogelauer M, Seligson DB et al (2013) Histone acetylation regulates intracellular pH. Mol Cell 49:310-321
    McCabe MT, Ott HM, Ganji G, Korenchuk S, Thompson C, Van Aller GS, Liu Y, Graves AP, Della Pietra A, Diaz E et al (2012) EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature 492:108-112
    McCarthy N (2013) LEUKAEMIA knowing left from right. Nat Rev Cancer 13:220-220
    McDonald OG, Li X, Saunders T, Tryggvadottir R, Mentch SJ, Warmoes MO, Word AE, Carrer A, Salz TH, Natsume S et al (2017) Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis. Nat Genet 49:367-376
    McGrath J, Trojer P (2015) Targeting histone lysine methylation in cancer. Pharmacol Ther 150:1-22
    Mentch SJ, Mehrmohamadi M, Huang L, Liu XJ, Gupta D, Mattocks D, Padilla PG, Ables G, Bamman MM, Thalacker-Mercer AE et al (2015) Histone methylation dynamics and gene regulation occur through the sensing of one-carbon metabolism. Cell Metab 22:861-873
    Mertz JA, Conery AR, Bryant BM, Sandy P, Balasubramanian S, Mele DA, Bergeron L, Sims RJ (2011) Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci USA 108:16669-16674
    Merza M, Hartman H, Rahman M, Hwaiz R, Zhang EM, Renstrom E, Luo LT, Morgelin M, Regner S, Thorlacius H (2015) Neutrophil extracellular traps induce trypsin activation, inflammation, and tissue damage in mice with severe acute pancreatitis. Gastroenterology 149:1920-1931
    Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang JJ, Hiller K, Jewell CM, Johnson ZR, Irvine DJ, Guarente L et al (2012) Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 481:380
    Mews P, Donahue G, Drake AM, Luczak V, Abel T, Berger SL (2017) Acetyl-CoA synthetase regulates histone acetylation and hippocampal memory. Nature 546:381-386
    Mi WY, Gu YC, Han CF, Liu HY, Fan QO, Zhang XL, Cong Q, Yu WG (2011) O-GlcNAcylation is a novel regulator of lung and colon cancer malignancy. Biochim Biophys Acta 1812:514-519
    Michelakis ED, Sutendra G, Dromparis P, Webster L, Haromy A, Niven E, Maguire C, Gammer TL, Mackey JR, Fulton D et al (2010) Metabolic modulation of glioblastoma with dichloroacetate. Sci Transl Med 2:31ra34
    Michelucci A, Cordes T, Ghelfi J, Pailot A, Reiling N, Goldmann O, Binz T, Wegner A, Tallam A, Rausell A et al (2013) Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc Natl Acad Sci USA 110:7820-7825
    Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D, Zaslona Z, Jedrychowski MP, Costa ASH, Higgins M, Hams E et al (2018) Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature 556:113-117
    Monti M, De Rosa V, Iommelli F, Carriero MV, Terlizzi C, Camerlingo R, Belli S, Fonti R, Di Minno G, and Del Vecchio S (2018) Neutrophil extracellular traps as an adhesion substrate for different tumor cells expressing RGD-binding integrins. Int J Mol Sci 19
    Morrish F, Noonan J, Perez-Olsen C, Gafken PR, Fitzgibbon M, Kelleher J, VanGilst M, Hockenbery D (2010) Myc-dependent mitochondrial generation of acetyl-CoA contributes to fatty acid biosynthesis and histone acetylation during cell cycle entry. J Biol Chem 285:36267-36274
    Moscarello MA, Mastronardi FG, Wood DD (2007) The role of citrullinated proteins suggests a novel mechanism in the pathogenesis of multiple sclerosis. Neurochem Res 32:251-256
    Moss TJ, Wallrath LL (2007) Connections between epigenetic gene silencing and human disease. Mutat Res 618:163-174
    Mullen AR, Wheaton WW, Jin ES, Chen PH, Sullivan LB, Cheng T, Yang YF, Linehan WM, Chandel NS, DeBerardinis RJ (2012) Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 481:385
    Murphy MP, O'Neill LAJ (2018) Krebs cycle reimagined:the emerging roles of succinate and itaconate as signal transducers. Cell 174:780-784
    Musselman CA, Khorasanizadeh S, Kutateladze TG (2014) Towards understanding methyllysine readout. Biochim Biophys Acta 1839:686-693
    Muthusamy T, Cordes T, Handzlik MK, You L, Lim EW, Gengatharan J, Pinto AFM, Badur MG, Kolar MJ, Wallace M et al (2020) Serine restriction alters sphingolipid diversity to constrain tumour growth. Nature
    Nair S, Huynh JP, Lampropoulou V, Loginicheva E, Esaulova E, Gounder AP, Boon ACM, Schwarzkopf EA, Bradstreet TR, Edelson BT et al (2018) Irg1 expression in myeloid cells prevents immunopathology during M. tuberculosis infection. J Exp Med 215:1035-1045
    Namgaladze D, Zukunft S, Schnutgen F, Kurrle N, Fleming I, Fuhrmann D, Brune B (2018) Polarization of human macrophages by interleukin-4 does not require ATP-citrate lyase. Front Immunol 9
    Nanduri J, Semenza GL, Prabhakar NR (2017) Epigenetic changes by DNA methylation in chronic and intermittent hypoxia. Am J Physiol 313:L1096-L1100
    Nencioni A, Caffa I, Cortellino S, Longo VD (2018) Fasting and cancer:molecular mechanisms and clinical application. Nat Rev Cancer 18:707-719
    Newman JC, Verdin E (2014a) beta-Hydroxybutyrate:much more than a metabolite. Diabetes Res Clin Pract 106:173-181
    Newman JC, Verdin E (2014b) Ketone bodies as signaling metabolites. Trends Endocrinol Metab 25:42-52
    Newman JC, Verdin E (2017) beta-Hydroxybutyrate:a signaling metabolite. Annu Rev Nutr 37(37):51-76
    Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S, Chung CW, Chandwani R, Marazzi I, Wilson P, Coste H et al (2010) Suppression of inflammation by a synthetic histone mimic. Nature 468:1119-1123
    Nicolas E, Roumillac C, Trouche D (2003) Balance between acetylation and methylation of histone H3 lysine 9 on the E2F-responsive dihydrofolate reductase promoter. Mol Cell Biol 23:1614-1622
    Nonnenmacher Y, Hiller K (2018) Biochemistry of proinflammatory macrophage activation. Cell Mol Life Sci 75:2093-2109
    Nowak SJ, Corces VG (2004) Phosphorylation of histone H3:a balancing act between chromosome condensation and transcriptional activation. Trends Genet 20:214-220
    Obata F, Kuranaga E, Tomioka K, Ming M, Takeishi A, Chen CH, Soga T, Miura M (2014) Necrosis-driven systemic immune response alters SAM metabolism through the FOXO-GNMT axis. Cell Rep 7:821-833
    Oermann EK, Wu J, Guan KL, Xiong Y (2012) Alterations of metabolic genes and metabolites in cancer. Semin Cell Dev Biol 23:370-380
    Oldham WM, Clish CB, Yang Y, Loscalzo J (2015) Hypoxia-mediated Increases in L-2-hydroxyglutarate coordinate the metabolic response to reductive stress. Cell Metab 22:291-303
    Olson LE, Tollkuhn J, Scafoglio C, Krones A, Zhang J, Ohgi KA, Wu W, Taketo MM, Kemler R, Grosschedl R et al (2006) Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination. Cell 125:593-605
    Onakpoya I, Hung SK, Perry R, Wider B, Ernst E (2011) The use of garcinia extract (hydroxycitric acid) as a weight loss supplement:a systematic review and meta-analysis of randomised clinical trials. J Obes 2011:
    O'Neill LAJ, Artyomov MN (2019) Itaconate:the poster child of metabolic reprogramming in macrophage function. Nat Rev Immunol 19:273-281
    O'Neill LAJ, Pearce EJ (2016) Immunometabolism governs dendritic cell and macrophage function. J Exp Med 213:15-23
    Osinalde N, Mitxelena J, Sanchez-Quiles V, Akimov V, Aloria K, Arizmendi JM, Zubiaga AM, Blagoev B, Kratchmarova I (2016) Nuclear phosphoproteomic screen uncovers ACLY as mediator of IL-2-induced proliferation of CD4(+) T lymphocytes. Mol Cell Proteomics 15:2076-2092
    Pan PW, Feldman JL, Devries MK, Dong A, Edwards AM, Denu JM (2011) Structure and biochemical functions of SIRT6. J Biol Chem 286:14575-14587
    Pan J, Zhao XY, Lin CN, Xu HC, Yin ZL, Liu TZ, Zhang SZ (2014) Immune responsive gene 1, a novel oncogene, increases the growth and tumorigenicity of glioma. Oncol Rep 32:1957-1966
    Pan M, Reid MA, Lowman XH, Kulkarni RP, Tran TQ, Liu XJ, Yang Y, Hernandez-Davies JE, Rosales KK, Li HQ et al (2016) Regional glutamine deficiency in tumours promotes dedifferentiation through inhibition of histone demethylation. Nat Cell Biol 18:1090-1101
    Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC (2006) HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 3:187-197
    Papathanassiu AE, Ko JH, Imprialou M, Bagnati M, Srivastava PK, Vu HA, Cucchi D, McAdoo SP, Ananieva EA, Mauro C et al (2017) BCAT1 controls metabolic reprogramming in activated human macrophages and is associated with inflammatory diseases. Nat Commun 8
    Park J, Chen Y, Tishkoff DX, Peng C, Tan MJ, Dai LZ, Xie ZY, Zhang Y, Zwaans BMM, Skinner ME et al (2013) SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. Mol Cell 50:919-930
    Parker SJ, Metallo CM (2016) Chasing one-carbon units to understand the role of serine in epigenetics. Mol Cell 61:185-186
    Parker CW, Kern M, Eisen HN (1962) Polyfunctional dinitrophenyl haptens as reagents for elicitation of immediate type allergic skin responses. J Exp Med 115:789-801
    Parsa S, Ortega-Molina A, Ying H-Y, Jiang M, Teater M, Wang J, Zhao C, Reznik E, Pasion JP, Kuo D et al (2020) The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing. Nature Cancer 1:653-664
    Parsons DW, Jones S, Zhang XS, Lin JCH, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807-1812
    Pastor WA, Aravind L, Rao A (2013) TETonic shift:biological roles of TET proteins in DNA demethylation and transcription. Nat Rev Mol Cell Biol 14:341-356
    Patel MS, Nemeria NS, Furey W, Jordan F (2014) The pyruvate dehydrogenase complexes:structure-based function and regulation. J Biol Chem 289:16615-16623
    Pavlova NN, Thompson CB (2016) The emerging hallmarks of cancer metabolism. Cell Metab 23:27-47
    Pearce NJ, Yates JW, Berkhout TA, Jackson B, Tew D, Boyd H, Camilleri P, Sweeney P, Gribble AD, Shaw A et al (1998) The role of ATP citrate-lyase in the metabolic regulation of plasma lipids-hypolipidaemic effects of SB-204990, a lactone prodrug of the potent ATP citrate-lyase inhibitor SB-201076. Biochem J 334:113-119
    Pearce EL, Walsh MC, Cejas PJ, Harms GM, Shen H, Wang LS, Jones RG, Choi YW (2009) Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 460:103-U118
    Perez-Chacon G, Astudillo AM, Balgoma D, Balboa MA, Balsinde J (2009) Control of free arachidonic acid levels by phospholipases A2 and lysophospholipid acyltransferases. Biochim Biophys Acta 1791:1103-1113
    Pietrocola F, Galluzzi L, Bravo-San Pedro JM, Madeo F, Kroemer G (2015) Acetyl Coenzyme A:a central metabolite and second messenger. Cell Metab 21:805-821
    Pineiro M, Gonzalez PJ, Hernandez F, Palacian E (1991) Interaction of RNA polymerase II with acetylated nucleosomal core particles. Biochem Biophys Res Commun 177:370-376
    Pineiro M, Hernandez F, Palacian E (1992) Succinylation of histone amino groups facilitates transcription of nucleosomal cores. Biochim Biophys Acta 1129:183-187
    Poillet-Perez L, Xie XQ, Zhan L, Yang Y, Sharp DW, Hu ZS, Su XY, Maganti A, Jiang C, Lu WY et al (2018) Autophagy maintains tumour growth through circulating arginine. Nature 563:569-573
    Poli V, Fagnocchi L, Fasciani A, Cherubini A, Mazzoleni S, Ferrillo S, Miluzio A, Gaudioso G, Vaira V, Turdo A et al (2018) MYC-driven epigenetic reprogramming favors the onset of tumorigenesis by inducing a stem cell-like state (vol 9, 1024, 2018). Nat Commun 9
    Polletta L, Vernucci E, Carnevale I, Arcangeli T, Rotili D, Palmerio S, Steegborn C, Nowak T, Schutkowski M, Pellegrini L et al (2015) SIRT5 regulation of ammonia-induced autophagy and mitophagy. Autophagy 11:253-270
    Poole CJ, van Riggelen J (2017) MYC-master regulator of the cancer epigenome and transcriptome. Genes (Basel) 8
    Prickaerts P, Adriaens ME, van den Beucken T, Koch E, Dubois L, Dahlmans VEH, Gits C, Evelo CTA, Chan-Seng-Yue M, Wouters BG et al (2016) Hypoxia increases genome-wide bivalent epigenetic marking by specific gain of H3K27me3. Epigenet Chromatin 9
    Prigent C, Dimitrov S (2003) Phosphorylation of serine 10 in histone H3, what for? J Cell Sci 116:3677-3685
    Pritzker LB, Joshi S, Gowan JJ, Harauz G, Moscarello MA (2000) Deimination of myelin basic protein. 1. Effect of deimination of arginyl residues of myelin basic protein on its structure and susceptibility to digestion by cathepsin D. Biochemistry 39:5374-5381
    Pufulete M, Al-Ghnaniem R, Khushal A, Appleby P, Harris N, Gout S, Emery PW, Sanders TA (2005) Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma. Gut 54:648-653
    Qi H, Ning X, Yu C, Ji X, Jin Y, McNutt MA, Yin Y (2019) Succinylation-dependent mitochondrial translocation of PKM2 promotes cell survival in response to nutritional stress. Cell Death Dis 10:170
    Qin W, Qin K, Zhang Y, Jia W, Chen Y, Cheng B, Peng L, Chen N, Liu Y, Zhou W et al (2019) S-glycosylation-based cysteine profiling reveals regulation of glycolysis by itaconate. Nat Chem Biol 15:983-991
    Qin W, Zhang Y, Tang H, Liu D, Chen Y, Liu Y, Wang C (2020) Chemoproteomic profiling of itaconation by bioorthogonal probes in inflammatory macrophages. J Am Chem Soc 142:10894-10898
    Rardin MJ, He WJ, Nishida Y, Newman JC, Carrico C, Danielson SR, Guo A, Gut P, Sahu AK, Li B et al (2013) SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks. Cell Metab 18:920-933
    Reid MA, Dai Z, Locasale JW (2017) The impact of cellular metabolism on chromatin dynamics and epigenetics. Nat Cell Biol 19:1298-1306
    Ren J, Singh BN, Huang Q, Li ZF, Gao Y, Mishra P, Hwa YL, Li JP, Dowdy SC, Jiang SW (2011) DNA hypermethylation as a chemotherapy target. Cell Signal 23:1082-1093
    Reytor E, Perez-Miguelsanz J, Alvarez L, Perez-Sala D, Pajares MA (2009) Conformational signals in the C-terminal domain of methionine adenosyltransferase I/III determine its nucleocytoplasmic distribution. FASEB J 23:3347-3360
    Richie CT, Golden A (2005) Chromosome segregation:Aurora B gets tousled. Curr Biol 15:R379-R382
    Richon VM, Emiliani S, Verdin E, Webb Y, Breslow R, Rifkind RA, Marks PA (1998) A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. Proc Natl Acad Sci USA 95:3003-3007
    Riggs MG, Whittaker RG, Neumann JR, Ingram VM (1977) n-Butyrate causes histone modification in HeLa and friend erythroleukaemia cells. Nature 268:462-464
    Roediger WE (1982) Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology 83:424-429
    Rohle D, Popovici-Muller J, Palaskas N, Turcan S, Grommes C, Campos C, Tsoi J, Clark O, Oldrini B, Komisopoulou E et al (2013) An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science 340:626-630
    Romano KA, Martinez-Del Campo A, Kasahara K, Chittim CL, Vivas EI, Amador-Noguez D, Balskus EP, Rey FE (2017) Metabolic, epigenetic, and transgenerational effects of gut bacterial choline consumption. Cell Host Microbe 22(279-290):
    Ruan HB, Han XM, Li MD, Singh JP, Qian K, Azarhoush S, Zhao L, Bennett AM, Samuel VT, Wu J et al (2012) O-GlcNAc transferase/host cell factor C1 complex regulates gluconeogenesis by modulating PGC-1 alpha stability. Cell Metab 16:226-237
    Ruan HB, Nie YZ, Yang XY (2013) Regulation of protein degradation by O-GlcNAcylation:crosstalk with ubiquitination. Mol Cell Proteomics 12:3489-3497
    Ruderman NB, Xu XJ, Nelson L, Cacicedo JM, Saha AK, Lan F, Ido Y (2010) AMPK and SIRT1:a long-standing partnership? Am J Physiol-Endocrinol Metab 298:E751-E760
    Ruetz M, Campanello GC, Purchal M, Shen HY, McDevitt L, Gouda H, Wakabayashi S, Zhu JH, Rubin EJ, Warncke K et al (2019) Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair. Science 366:589-593
    Rufer AC, Thoma R, Hennig M (2009) Structural insight into function and regulation of carnitine palmitoyltransferase. Cell Mol Life Sci 66:2489-2501
    Rzem R, Vincent MF, Schaftingen E, Veiga-da-Cunha M (2007) L-2-Hydroxyglutaric aciduria, a defect of metabolite repair. J Inherit Metab Dis 30:681-689
    Sabari BR, Zhang D, Allis CD, Zhao YM (2017) Metabolic regulation of gene expression through histone acylations. Nat Rev Mol Cell Biol 18:90-101
    Sadakierska-Chudy A, Filip M (2015) A comprehensive view of the epigenetic landscape. Part II:Histone post-translational modification, nucleosome level, and chromatin regulation by ncRNAs. Neurotox Res 27:172-197
    Sakabe K, Wang Z, Hart GW (2010) Beta-N-acetylglucosamine (O-GlcNAc) is part of the histone code. Proc Natl Acad Sci USA 107:19915-19920
    Sakata SF, Shelly LL, Ruppert S, Schutz G, Chou JY (1993) Cloning and expression of murine S-adenosylmethionine synthetase. J Biol Chem 268:13978-13986
    Saldana-Meyer R, Recillas-Targa F (2011) Transcriptional and epigenetic regulation of the p53 tumor suppressor gene. Epigenetics 6:1068-1077
    Salvesen HB, MacDonald N, Ryan A, Jacobs IJ, Lynch ED, Akslen LA, Das S (2001) PTEN methylation is associated with advanced stage and microsatellite instability in endometrial carcinoma. Int J Cancer 91:22-26
    Sassone-Corsi P, Mizzen CA, Cheung P, Crosio C, Monaco L, Jacquot S, Hanauer A, Allis CD (1999) Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3. Science 285:886-891
    Scheppach W, Weiler F (2004) The butyrate story:old wine in new bottles? Curr Opin Clin Nutr Metab Care 7:563-567
    Schmitt AM, Schmid S, Rudolph T, Anlauf M, Prinz C, Kloppel G, Moch H, Heitz PU, Komminoth P, Perren A (2009) VHL inactivation is an important pathway for the development of malignant sporadic pancreatic endocrine tumors. Endocr Relat Cancer 16:1219-1227
    Schug ZT, Peck B, Jones DT, Zhang QF, Grosskurth S, Alam IS, Goodwin LM, Smethurst E, Mason S, Blyth K et al (2015) Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer Cell 27:57-71
    Sciacovelli M, Goncalves E, Johnson TI, Zecchini VR, da Costa ASH, Gaude E, Drubbel AV, Theobald SJ, Abbo SR, Tran MGB et al (2016) Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition (vol 537, pg 544, 2016). Nature 540
    Seligson DB, Horvath S, Shi T, Yu H, Tze S, Grunstein M, Kurdistani SK (2005) Global histone modification patterns predict risk of prostate cancer recurrence. Nature 435:1262-1266
    Seligson DB, Horvath S, McBrian MA, Mah V, Yu H, Tze S, Wang Q, Chia D, Goodglick L, Kurdistani SK (2009) Global levels of histone modifications predict prognosis in different cancers. Am J Pathol 174:1619-1628
    Serefidou M, Venkatasubramani AV, Imhof A (2019) The impact of one carbon metabolism on histone methylation. Front Genet 10
    Shan CL, Elf S, Ji QJ, Kang HB, Zhou L, Hitosugi T, Jin LT, Lin RT, Zhang L, Seo JH et al (2014) Lysine acetylation activates 6-phosphogluconate dehydrogenase to promote tumor growth. Mol Cell 55:552-565
    Shen H, Campanello GC, Flicker D, Grabarek Z, Hu J, Luo C, Banerjee R, Mootha VK (2017) The human knockout gene CLYBL connects itaconate to vitamin B12. Cell 171(771-782):
    Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119:941-953
    Shi Y, Tomic J, Wen F, Shaha S, Bahlo A, Harrison R, Dennis JW, Williams R, Gross BJ, Walker S et al (2010) Aberrant O-GlcNAcylation characterizes chronic lymphocytic leukemia. Leukemia 24:1588-1598
    Shi FT, Kim H, Lu W, He Q, Liu D, Goodell MA, Wan M, Songyang Z (2013) Ten-eleven translocation 1 (Tet1) is regulated by O-linked N-acetylglucosamine transferase (Ogt) for target gene repression in mouse embryonic stem cells. J Biol Chem 288:20776-20784
    Shi J, Gu JH, Dai CL, Gu J, Jin X, Sun J, Iqbal K, Liu F, Gong CX (2015) O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling. Sci Rep 5:14500
    Shi WY, Yang X, Huang B, Shen WH, Liu L (2017) NOK mediates glycolysis and nuclear PDC associated histone acetylation. Front Biosci 22:1792-1804
    Shim EH, Livi CB, Rakheja D, Tan J, Benson D, Parekh V, Kho EY, Ghosh AP, Kirkman R, Velu S et al (2014) L-2-hydroxyglutarate:an epigenetic modifier and putative oncometabolite in renal cancer. Cancer Discov 4:1290-1298
    Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, Grueter CA, Lim H, Saunders LR, Stevens RD et al (2013) Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339:211-214
    Shin JH, Yang JY, Jeon BY, Yoon YJ, Cho SN, Kang YH, Ryu DH, Hwang GS (2011) (1)H NMR-based metabolomic profiling in mice infected with Mycobacterium tuberculosis. J Proteome Res 10:2238-2247
    Shu LM, Khor TO, Lee JH, Boyanapalli SSS, Huang Y, Wu TY, Saw CLL, Cheung KL, Kong ANT (2011) Epigenetic CpG demethylation of the promoter and reactivation of the expression of neurog1 by curcumin in prostate LNCaP cells. Aaps J 13:606-614
    Shyh-Chang N, Locasale JW, Lyssiotis CA, Zheng YX, Teo RY, Ratanasirintrawoot S, Zhang J, Onder T, Unternaehrer JJ, Zhu H et al (2013) Influence of threonine metabolism on S-adenosylmethionine and histone methylation. Science 339:222-226
    Siedlecki P, Boy RG, Comagic S, Schirrmacher R, Wiessler M, Zielenkiewicz P, Suhai S, Lyko F (2003) Establishment and functional validation of a structural homology model for human DNA methyltransferase 1. Biochem Biophys Res Commun 306:558-563
    Singer MS, Kahana A, Wolf AJ, Meisinger LL, Peterson SE, Goggin C, Mahowald M, Gottschling DE (1998) Identification of high-copy disruptors of telomeric silencing in Saccharomyces cerevisiae. Genetics 150:613-632
    Singh N, Duenas-Gonzalez A, Lyko F, Medina-Franco JL (2009a) Molecular modeling and molecular dynamics studies of hydralazine with human DNA methyltransferase 1. ChemMedChem 4:792-799
    Singh RK, Kabbaj MH, Paik J, Gunjan A (2009b) Histone levels are regulated by phosphorylation and ubiquitylation-dependent proteolysis. Nat Cell Biol 11:925-933
    Singh BN, Shankar S, Srivastava RK (2011) Green tea catechin, epigallocatechin-3-gallate (EGCG):mechanisms, perspectives and clinical applications. Biochem Pharmacol 82:1807-1821
    Singh JP, Zhang K, Wu J, Yang X (2015) O-GlcNAc signaling in cancer metabolism and epigenetics. Cancer Lett 356:244-250
    Sivanand S, Rhoades S, Jiang Q, Lee JV, Benci J, Zhang J, Yuan S, Viney I, Zhao S, Carrer A et al (2017) Nuclear acetyl-CoA production by ACLY promotes homologous recombination. Mol Cell 67(252-265):
    Slawson C, Hart GW (2011) O-GlcNAc signalling:implications for cancer cell biology. Nat Rev Cancer 11:678-684
    Slawson C, Pidala J, Potter R (2001) Increased N-acetyl-beta-glucosaminidase activity in primary breast carcinomas corresponds to a decrease in N-acetylglucosamine containing proteins. Biochim Biophys Acta 1537:147-157
    Smestad J, Erber L, Chen Y, Maher LJ (2018) Chromatin succinylation correlates with active gene expression and is perturbed by defective TCA cycle metabolism. Iscience 2:63-75
    Soesanto YA, Luo B, Jones D, Taylor R, Gabrielsen JS, Parker G, McClain DA (2008) Regulation of Akt signaling by O-GlcNAc in euglycemia. Am J Physiol Endocrinol Metab 295:E974-980
    Soloaga A, Thomson S, Wiggin GR, Rampersaud N, Dyson MH, Hazzalin CA, Mahadevan LC, Arthur JS (2003) MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14. EMBO J 22:2788-2797
    Song H, Ma J, Bian ZX, Chen SH, Zhu JB, Wang J, Huang N, Yin MZ, Sun FY, Xu M et al (2019) Global profiling of O-GlcNAcylated and/or phosphorylated proteins in hepatoblastoma. Signal Transduct Target Ther 4
    Soria JC, Lee HY, Lee JI, Wang L, Issa JP, Kemp BL, Liu DD, Kurie JM, Mao L, Khuri FR (2002) Lack of PTEN expression in non-small cell lung cancer could be related to promoter methylation. Clin Cancer Res 8:1178-1184
    Sorm F, Piskala A, Cihak A, Vesely J (1964) 5-Azacytidine, a new, highly effective cancerostatic. Experientia 20:202-203
    Sreedhar A, Wiese EK, Hitosugi T (2020) Enzymatic and metabolic regulation of lysine succinylation. Genes Dis 7:166-171
    Stafford JM, Lee CH, Voigt P, Descostes N, Saldana-Meyer R, Yu JR, Leroy G, Oksuz O, Chapman JR, Suarez F et al (2018) Multiple modes of PRC2 inhibition elicit global chromatin alterations in H3K27M pediatric glioma. Sci Adv 4
    Steinberg GR, Carling D (2019) AMP-activated protein kinase:the current landscape for drug development. Nat Rev Drug Discov 18:527-551
    Stine ZE, Walton ZE, Altman BJ, Hsieh AL, Dang CV (2015) MYC, metabolism, and cancer. Cancer Discov 5:1024-1039
    Stram AR, Payne RM (2016) Post-translational modifications in mitochondria:protein signaling in the powerhouse. Cell Mol Life Sci 73:4063-4073
    Strelko CL, Lu WY, Dufort FJ, Seyfried TN, Chiles TC, Rabinowitz JD, Roberts MF (2011) Itaconic acid is a mammalian metabolite induced during macrophage activation. J Am Chem Soc 133:16386-16389
    Su CH, Shann YJ, Hsu MT (2009) p53 chromatin epigenetic domain organization and p53 transcription. Mol Cell Biol 29:93-103
    Sugimoto M, Sakagami H, Yokote Y, Onuma H, Kaneko M, Mori M, Sakaguchi Y, Soga T, Tomita M (2011) Non-targeted metabolite profiling in activated macrophage secretion. Metabolomics 8:624-633
    Sugimura T, Birnbaum SM, Winitz M, Greenstein JP (1959) Quantitative nutritional studies with water-soluble, chemically defined diets. VII. Nitrogen balance in normal and tumor-bearing rats following forced feeding. Arch Biochem Biophys 81:439-447
    Sulkowski PL, Corso CD, Robinson ND, Scanlon SE, Purshouse KR, Bai H, Liu Y, Sundaram RK, Hegan DC, Fons NR et al (2017) 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Sci Transl Med 9
    Sulkowski PL, Sundaram RK, Oeck S, Corso CD, Liu Y, Noorbakhsh S, Niger M, Boeke M, Ueno D, Kalathil AN et al (2018) Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair. Nat Genet 50:1086-1092
    Sulkowski PL, Oeck S, Dow J, Economos NG, Mirfakhraie L, Liu Y, Noronha K, Bao X, Li J, Shuch BM et al (2020) Oncometabolites suppress DNA repair by disrupting local chromatin signalling. Nature 582:586-591
    Sun LC, Gao P (2017) Reproducibility in cancer biology:small molecules remain on target for c-Myc. Elife 6
    Sun LC, Song LB, Wan QF, Wu GW, Li XH, Wang YH, Wang J, Liu ZJ, Zhong XY, He XP et al (2015) cMyc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrient deprivation conditions. Cell Res 25:429-444
    Sun LC, Suo CX, Li ST, Zhang HF, Gao P (2018) Metabolic reprogramming for cancer cells and their microenvironment:beyond the Warburg effect. Biochim Biophys Acta 1870:51-66
    Sutendra G, Kinnaird A, Dromparis P, Paulin R, Stenson TH, Haromy A, Hashimoto K, Zhang N, Flaim E, Michelakis ED (2014) A nuclear pyruvate dehydrogenase complex is important for the generation of acetyl-CoA and histone acetylation. Cell 158:84-97
    Takahashi H, McCaffery JM, Irizarry RA, Boeke JD (2006) Nucleocytosolic acetyl-coenzyme A synthetase is required for histone acetylation and global transcription. Mol Cell 23:207-217
    Takawa M, Masuda K, Kunizaki M, Daigo Y, Takagi K, Iwai Y, Cho HS, Toyokawa G, Yamane Y, Maejima K et al (2011) Validation of the histone methyltransferase EZH2 as a therapeutic target for various types of human cancer and as a prognostic marker. Cancer Sci 102:1298-1305
    Takusagawa F, Kamitori S, Markham GD (1996) Structure and function of S-adenosylmethionine synthetase:crystal structures of S-adenosylmethionine synthetase with ADP, BrADP, and PPi at 28 angstroms resolution. Biochemistry 35:2586-2596
    Tallam A, Perumal TM, Antony PM, Jager C, Fritz JV, Vallar L, Balling R, del Sol A, Michelucci A (2016) Gene regulatory network inference of immunoresponsive gene 1 (IRG1) identifies interferon regulatory factor 1 (IRF1) as its transcriptional regulator in mammalian macrophages. PLoS ONE 11
    Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, Frezza C, Bernard NJ, Kelly B, Foley NH et al (2013) Succinate is an inflammatory signal that induces IL-1 beta through HIF-1 alpha. Nature 496:238-242
    Taplin ME, Hussain A, Shore ND, Bradley B, Trojer P, Lebedinsky C, Senderowicz AM, Antonarakis ES (2018) A phase 1b/2 study of CPI-1205, a small molecule inhibitor of EZH2, combined with enzalutamide (E) or abiraterone/prednisone (A/P) in patients with metastatic castration resistant prostate cancer (mCRPC). J Clin Oncol 36
    Thalin C, Lundstrom S, Seignez C, Daleskog M, Lundstrom A, Henriksson P, Helleday T, Phillipson M, Wallen H, Demers M (2018). Citrullinated histone H3 as a novel prognostic blood marker in patients with advanced cancer. PLoS ONE 13
    Thompson CB (2019) Cancer cell metabolism:reexamining the regulation of anabolic growth in health and disease. Faseb J 33
    Tohme S, Yazdani HO, Al-Khafaji AB, Chidi AP, Loughran P, Mowen K, Wang YM, Simmons RL, Huang H, Tsung A (2016) Neutrophil extracellular traps promote the development and progression of liver metastases after surgical stress. Cancer Res 76:1367-1380
    Topper MJ, Vaz M, Chiappinelli KB, DeStefano Shields CE, Niknafs N, Yen RC, Wenzel A, Hicks J, Ballew M, Stone M et al (2017) Epigenetic therapy ties MYC depletion to reversing immune evasion and treating lung cancer. Cell 171(1284-1300):
    Trojan J, Brieger A, Raedle J, Esteller M, Zeuzem S (2000) 5'-CpG island methylation of the LKB1/STK11 promoter and allelic loss at chromosome 19p13.3 in sporadic colorectal cancer. Gut 47:272-276
    Tyrakis PA, Palazon A, Macias D, Lee KL, Phan AT, Velica P, You J, Chia GS, Sim J, Doedens A et al (2016) S-2-hydroxyglutarate regulates CD8(+) T-lymphocyte fate. Nature 540:236-241
    Uddin MJ, Joe Y, Kim SK, Jeong SO, Ryter SW, Pae HO, Chung HT (2016) IRG1 induced by heme oxygenase-1/carbon monoxide inhibits LPS-mediated sepsis and pro-inflammatory cytokine production. Cell Mol Immunol 13:170-179
    Ulivi P, Mercatali L, Casoni GL, Scarpi E, Bucchi L, Silvestrini R, Sanna S, Monteverde M, Amadori D, Poletti V et al (2013) Multiple marker detection in peripheral blood for NSCLC diagnosis. PLoS ONE 8
    van den Berg MA, de Jong-Gubbels P, Kortland CJ, van Dijken JP, Pronk JT, Steensma HY (1996) The two acetyl-coenzyme A synthetases of Saccharomyces cerevisiae differ with respect to kinetic properties and transcriptional regulation. J Biol Chem 271:28953-28959
    Van Quickelberghe E, Martens A, Goeminne LJE, Clement L, van Loo G, Gevaert K (2018) Identification of immune-responsive gene 1 (IRG1) as a target of A20. J Proteome Res 17:2182-2191
    Vanharanta S, Shu W, Brenet F, Hakimi AA, Heguy A, Viale A, Reuter VE, Hsieh JJ, Scandura JM, Massague J (2013) Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer. Nat Med 19:50-56
    Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, Ghosh D, Pienta KJ, Sewalt RGAB, Otte AP et al (2002) The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419:624-629
    Varambally S, Cao Q, Mani RS, Shankar S, Wang XS, Ateeq B, Laxman B, Cao XH, Jing XJ, Ramnarayanan K et al (2008) Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in Cancer. Science 322:1695-1699
    Vella P, Scelfo A, Jammula S, Chiacchiera F, Williams K, Cuomo A, Roberto A, Christensen J, Bonaldi T, Helin K et al (2013) Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells. Mol Cell 49:645-656
    Ventura M, Mateo F, Serratosa J, Salaet I, Carujo S, Bachs O, Pujol MJ (2010) Nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase is regulated by acetylation. Int J Biochem Cell Biol 42:1672-1680
    Verdin E (2015) NAD(+) in aging, metabolism, and neurodegeneration. Science 350:1208-1213
    Verschueren KHG, Blanchet C, Felix J, Dansercoer A, De Vos D, Bloch Y, Van Beeumen J, Svergun D, Gutsche I, Savvides SN et al (2019) Structure of ATP citrate lyase and the origin of citrate synthase in the Krebs cycle. Nature 568:571-575
    Vidali G, Boffa LC, Bradbury EM, Allfrey VG (1978) Butyrate suppression of histone deacetylation leads to accumulation of multiacetylated forms of histones H3 and H4 and increased DNase I sensitivity of the associated DNA sequences. Proc Natl Acad Sci USA 75:2239-2243
    Volkel P, Dupret B, Le Bourhis X, Angrand PO (2015) Diverse involvement of EZH2 in cancer epigenetics. Am J Transl Res 7:175-193
    Vrba L, Junk DJ, Novak P, Futscher BW (2008) p53 induces distinct epigenetic states at its direct target promoters. Bmc Genomics 9
    Wagener N, Macher-Goeppinger S, Pritsch M, Husing J, Hoppe-Seyler K, Schirmacher P, Pfitzenmaier J, Haferkamp A, Hoppe-Seyler F, Hohenfellner M (2010) Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma. Bmc Cancer 10
    Wang YP, Lei QY (2018) Metabolic recoding of epigenetics in cancer. Cancer Commun (Lond) 38:25
    Wang Y, Wysocka J, Sayegh J, Lee YH, Perlin JR, Leonelli L, Sonbuchner LS, McDonald CH, Cook RG, Dou Y et al (2004) Human PAD4 regulates histone arginine methylation levels via demethylimination. Science 306:279-283
    Wang J, Alexander P, Wu L, Hammer R, Cleaver O, McKnight SL (2009) Dependence of mouse embryonic stem cells on threonine catabolism. Science 325:435-439
    Wang YJ, Li PX, Wang S, Hu J, Chen XA, Wu JH, Fisher M, Oshaben K, Zhao N, Gu Y et al (2012) Anticancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy flux and the mammalian target of rapamycin complex 1 activity. J Biol Chem 287:25941-25953
    Wang F, Travins J, DeLaBarre B, Penard-Lacronique V, Schalm S, Hansen E, Straley K, Kernytsky A, Liu W, Gliser C et al (2013) Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science 340:622-626
    Wang F, Wang K, Xu W, Zhao SM, Ye D, Wang Y, Xu Y, Zhou LS, Chu YW, Zhang CP et al (2017a) SIRT5 desuccinylates and activates pyruvate kinase M2 to block macrophage IL-1 beta production and to prevent DSS-induced colitis in mice. Cell Rep 19:2331-2344
    Wang Y, Guo YR, Liu K, Yin Z, Liu R, Xia Y, Tan L, Yang P, Lee JH, Li XJ et al (2017b) KAT2A coupled with the alpha-KGDH complex acts as a histone H3 succinyltransferase. Nature 552:273-277
    Wang Y, Jin J, Chung MWH, Feng L, Sun HY, Hao Q (2018a) Identification of the YEATS domain of GAS41 as a pH-dependent reader of histone succinylation. Proc Natl Acad Sci USA 115:2365-2370
    Wang YG, Guo YR, Xing DM, Tao YJ, Lu ZM (2018b) Supramolecular assembly of KAT2A with succinyl-CoA for histone succinylation. Cell Discov 4
    Wang C, Zhang C, Li X, Shen J, Xu Y, Shi H, Mu X, Pan J, Zhao T, Li M et al (2019a) CPT1A-mediated succinylation of S100A10 increases human gastric cancer invasion. J Cell Mol Med 23:293-305
    Wang GX, Meyer JG, Cai WK, Softic S, Li ME, Verdin E, Newgard C, Schilling B, Kahn CR (2019b) Regulation of UCP1 and mitochondrial metabolism in brown adipose tissue by reversible succinylation. Mol Cell 74:844-857
    Ward PS, Patel J, Wise DR, Abdel-Wahab O, Bennett BD, Coller HA, Cross JR, Fantin VR, Hedvat CV, Perl AE et al (2010) The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17:225-234
    Watson JA, Watson CJ, McCann A, Baugh J (2010) Epigenetics, the epicenter of the hypoxic response. Epigenetics 5:293-296
    Weinert BT, Scholz C, Wagner SA, Iesmantavicius V, Su D, Daniel JA, Choudhary C (2013) Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. Cell Rep 4:842-851
    Weiss JM, Davies LC, Karwan M, Ileva L, Ozaki MK, Cheng RYS, Ridnour LA, Annunziata CM, Wink DA, McVicar DW (2018) Itaconic acid mediates crosstalk between macrophage metabolism and peritoneal tumors. J Clin Investig 128:3794-3805
    Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB (2009) ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324:1076-1080
    Williams NC, O'Neill LAJ (2018) A Role for the Krebs Cycle Intermediate Citrate in Metabolic Reprogramming in Innate Immunity and Inflammation. Front Immunol 9:141
    Williams NC, O'Neill LA (2020) ACLY-matizing macrophages to histone modification during immunometabolic reprogramming. Trends Immunol 41:93-94
    Williams SC, Karajannis MA, Chiriboga L, Golfinos JG, von Deimling A, Zagzag D (2011) R132H-mutation of isocitrate dehydrogenase-1 is not sufficient for HIF-1 alpha upregulation in adult glioma. Acta Neuropathol 121:279-281
    Wise DR, Ward PS, Shay JES, Cross JR, Gruber JJ, Sachdeva UM, Platt JM, DeMatteo RG, Simon MC, Thompson CB (2011) Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of alpha-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci USA 108:19611-19616
    Witalison EE, Thompson PR, Hofseth LJ (2015) Protein arginine deiminases and associated citrullination:physiological functions and diseases associated with dysregulation. Curr Drug Targets 16:700-710
    Wong CC, Qian Y, Yu J (2017) Interplay between epigenetics and metabolism in oncogenesis:mechanisms and therapeutic approaches. Oncogene 36:3359-3374
    Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430:686-689
    Wu GW, Yuan MQ, Shen SQ, Ma XY, Fang JW, Zhu LB, Sun LC, Liu ZJ, He XP, Huang D et al (2017) Menin enhances c-Myc-mediated transcription to promote cancer progression. Nat Commun 8
    Xia S, Lin R, Jin L, Zhao L, Kang HB, Pan Y, Liu S, Qian G, Qian Z, Konstantakou E et al (2017) Prevention of dietary-fat-fueled ketogenesis attenuates BRAF V600E tumor growth. Cell Metab 25:358-373
    Xiangyun Y, Xiaomin N, Linping G, Yunhua X, Ziming L, Yongfeng Y, Zhiwei C, Shun L (2017) Desuccinylation of pyruvate kinase M2 by SIRT5 contributes to antioxidant response and tumor growth. Oncotarget 8:6984-6993
    Xiao HB, Cao WX, Yin HR, Lin YZ, Ye SH (2001) Influence of L-methionine-deprived total parenteral nutrition with 5-fluorouracil on gastric cancer and host metabolism. World J Gastroenterol 7:698-701
    Xiao A, Li H, Shechter D, Ahn SH, Fabrizio LA, Erdjument-Bromage H, Ishibe-Murakami S, Wang B, Tempst P, Hofmann K et al (2009) WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity. Nature 457:57-62
    Xiao M, Yang H, Xu W, Ma S, Lin H, Zhu H, Liu L, Liu Y, Yang C, Xu Y et al (2012) Inhibition of alpha-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev 26:1326-1338
    Xie Z, Dai J, Dai L, Tan M, Cheng Z, Wu Y, Boeke JD, Zhao Y (2012) Lysine succinylation and lysine malonylation in histones. Mol Cell Proteomics 11:100-107
    Xie ZY, Zhang D, Chung DJ, Tang ZY, Huang H, Dai LZ, Qi SK, Li JY, Colak G, Chen Y et al (2016) Metabolic regulation of gene expression by histone lysine beta-hydroxybutyrylation. Mol Cell 62:194-206
    Xu Q, Li Y, Gao X, Kang K, Williams JG, Tong L, Liu J, Ji M, Deterding LJ, Tong X et al (2020) HNF4alpha regulates sulfur amino acid metabolism and confers sensitivity to methionine restriction in liver cancer. Nat Commun 11:3978
    Xu D, Shao F, Bian X, Meng Y, Liang T, Lu Z (2021) The evolving landscape of noncanonical functions of metabolic enzymes in cancer and other pathologies. Cell Metab 33:33-50
    Yadav T, Quivy JP, Almouzni G (2018) Chromatin plasticity:a versatile landscape that underlies cell fate and identity. Science 361:1332-1336
    Yan H, Parsons DW, Jin GL, McLendon R, Rasheed BA, Yuan WS, Kos I, Batinic-Haberle I, Jones S, Riggins GJ et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765-773
    Yang J (2019) Sweetly profiling the cysteinome. Nat Chem Biol 15:935-936
    Yang X, Qian K (2017) Protein O-GlcNAcylation:emerging mechanisms and functions. Nat Rev Mol Cell Biol 18:452-465
    Yang Y, Sauve AA (2016) NAD(+) metabolism:bioenergetics, signaling and manipulation for therapy. Biochim Biophys Acta 1864:1787-1800
    Yang M, Vousden KH (2016) Serine and one-carbon metabolism in cancer. Nat Rev Cancer 16:650-662
    Yang XY, Zhang FX, Kudlow JE (2002) Recruitment of O-GlcNAc transferase to promoters by corepressor mSin3A:coupling protein O-GlcNAcylation to transcriptional repression. Cell 110:69-80
    Yang HY, Yang T, Baur JA, Perez E, Matsui T, Carmona JJ, Lamming DW, Souza-Pinto NC, Bohr VA, Rosenzweig A et al (2007) Nutrient-sensitive mitochondrial NAD(+) levels dictate cell survival. Cell 130:1095-1107
    Yang CS, Wang X, Lu G, Picinich SC (2009) Cancer prevention by tea:animal studies, molecular mechanisms and human relevance. Nat Rev Cancer 9:429-439
    Yang CF, Sun WY, Cui W, Li XK, Yao J, Jia XY, Li CJ, Wu HJ, Hu ZY, Zou XM (2015) Procoagulant role of neutrophil extracellular traps in patients with gastric cancer. Int J Clin Exp Pathol 8:14075-14086
    Yao HJ, Li PX, Venters BJ, Zheng S, Thompson PR, Pugh BF, Wang YM (2008) Histone Arg modifications and p53 regulate the expression of OKL38, a mediator of apoptosis. J Biol Chem 283:20060-20068
    Ye D, Ma SH, Xiong Y, Guan KL (2013) R-2-hydroxyglutarate as the key effector of IDH mutations promoting oncogenesis. Cancer Cell 23:274-276
    Ye D, Guan KL, Xiong Y (2018) Metabolism, activity, and targeting of D- and L-2-hydroxyglutarates. Trends Cancer 4:151-165
    Yen K, Travins J, Wang F, David MD, Artin E, Straley K, Padyana A, Gross S, DeLaBarre B, Tobin E et al (2017) AG-221, a first-in-class therapy targeting acute myeloid leukemia harboring oncogenic IDH2 mutations. Cancer Discov 7:478-493
    Yi CH, Pan H, Seebacher J, Jang IH, Hyberts SG, Heffron GJ, Vander Heiden MG, Yang R, Li F, Locasale JW et al (2011) Metabolic regulation of protein N-alpha-acetylation by Bcl-xL promotes cell survival. Cell 146:607-620
    Yoo J, Medina-Franco JL (2011) Homology modeling, docking and structure-based pharmacophore of inhibitors of DNA methyltransferase. J Comput Aided Mol Des 25:555-567
    Yoo CB, Jeong S, Egger G, Liang GN, Phiasivongsa P, Tang CL, Redkar S, Jones PA (2007) Delivery of 5-aza-2'-deoxycytidine to cells using oligodeoxynucleotides. Cancer Res 67:6400-6408
    Yu J, Yu J, Rhodes DR, Tomlins SA, Cao X, Chen G, Mehra R, Wang X, Ghosh D, Shah RB et al (2007) A polycomb repression signature in metastatic prostate cancer predicts cancer outcome. Cancer Res 67:10657-10663
    Yu XH, Zhang DW, Zheng XL, Tang CK (2019) Itaconate:an emerging determinant of inflammation in activated macrophages. Immunol Cell Biol 97:134-141
    Yuan H, Han Y, Wang X, Li N, Liu Q, Yin Y, Wang H, Pan L, Li L, Song K et al (2020) SETD2 Restricts Prostate Cancer Metastasis by Integrating EZH2 and AMPK Signaling Pathways. Cancer Cell.
    Yun MY, Wu J, Workman JL, Li B (2011) Readers of histone modifications. Cell Res 21:564-578
    Yuzhalin AE (2019) Citrullination in cancer. Cancer Res 79:1274-1284
    Yuzhalin AE, Gordon-Weeks AN, Tognoli ML, Jones K, Markelc B, Konietzny R, Fischer R, Muth A, O'Neill E, Thompson PR et al (2018) Colorectal cancer liver metastatic growth depends on PAD4-driven citrullination of the extracellular matrix. Nat Commun 9
    Zaidi N, Swinnen JV, Smans K (2012) ATP-citrate lyase:a key player in cancer metabolism. Cancer Res 72:3709-3714
    Zamierowski MM, Wagner C (1977) Identification of folate binding proteins in rat liver. J Biol Chem 252:933-938
    Zeng JD, Wu WKK, Wang HY, Li XX (2019) Serine and one-carbon metabolism, a bridge that links mTOR signaling and DNA methylation in cancer. Pharmacol Res 149
    Zhang ZH, Tan MJ, Xie ZY, Dai LZ, Chen Y, Zhao YM (2011) Identification of lysine succinylation as a new post-translational modification. Nat Chem Biol 7:58-63
    Zhang Q, Liu X, Gao W, Li P, Hou J, Li J, Wong J (2014) Differential regulation of the ten-eleven translocation (TET) family of dioxygenases by O-linked beta-N-acetylglucosamine transferase (OGT). J Biol Chem 289:5986-5996
    Zhang W, Zhang SL, Hu X, Tam KY (2015) Targeting tumor metabolism for cancer treatment:is pyruvate dehydrogenase kinases (PDKs) a viable anticancer target? Int J Biol Sci 11:1390-1400
    Zhang D, Tang ZY, Huang H, Zhou GL, Cui C, Weng YJ, Liu WC, Kim S, Lee S, Perez-Neut M et al (2019a) Metabolic regulation of gene expression by histone lactylation. Nature 574:575-580
    Zhang XR, Cao RL, Niu JR, Yang SM, Ma HD, Zhao S, Li HT (2019b) Molecular basis for hierarchical histone de-beta-hydroxybutmlation by SIRT3. Cell Discov 5
    Zhang HF, Tang K, Ma JW, Zhou L, Liu JC, Zeng LP, Zhu LY, Xu PW, Chen J, Wei KK et al (2020) Ketogenesis-generated beta-hydroxybutyrate is an epigenetic regulator of CD8(+) T-cell memory development. Nat Cell Biol 22:18-25
    Zhao K, Miao H (2020) Targeting metabolic/epigenetic pathways:a potential strategy for cancer therapy in diffuse intrinsic pontine gliomas. Signal Transduct Target Ther 5:226
    Zhao G, Winkler ME (1996) A novel alpha-ketoglutarate reductase activity of the serA-encoded 3-phosphoglycerate dehydrogenase of Escherichia coli K-12 and its possible implications for human 2-hydroxyglutaric aciduria. J Bacteriol 178:232-239
    Zhao S, Lin Y, Xu W, Jiang W, Zha Z, Wang P, Yu W, Li Z, Gong L, Peng Y et al (2009) Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha. Science 324:261-265
    Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H et al (2010) Regulation of cellular metabolism by protein lysine acetylation. Science 327:1000-1004
    Zhao S, Torres A, Henry RA, Trefely S, Wallace M, Lee JV, Carrer A, Sengupta A, Campbell SL, Kuo YM et al (2016) ATP-citrate lyase controls a glucose-to-acetate metabolic switch. Cell Rep 17:1037-1052
    Zhao D, Li YY, Xiong XZ, Chen ZL, Li HT (2017) YEATS domain-A histone acylation reader in health and disease. J Mol Biol 429:1994-2002
    Zhao S, Zhang X, Li H (2018) Beyond histone acetylation-writing and erasing histone acylations. Curr Opin Struct Biol 53:169-177
    Zhao S, Jang C, Liu J, Uehara K, Gilbert M, Izzo L, Zeng XF, Trefely S, Fernandez S, Carrer A et al (2020) Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. Nature 579:586-591
    Zheng QF, Maksimovic I, Upad A, David Y (2020) Non-enzymatic covalent modifications:a new link between metabolism and epigenetics. Protein Cell 11:401-416
    Zhou LS, Wang F, Sun RQ, Chen XF, Zhang ML, Xu Q, Wang Y, Wang SW, Xiong Y, Guan KL et al (2016) SIRT5 promotes IDH2 desuccinylation and G6PD deglutarylation to enhance cellular antioxidant defense. EMBO Rep 17:811-822
    Zippo A, De Robertis A, Serafini R, Oliviero S (2007) PIM1-dependent phosphorylation of histone H3 at serine 10 is required for MYC-dependent transcriptional activation and oncogenic transformation. Nat Cell Biol 9:932
    Zuber J, Shi JW, Wang E, Rappaport AR, Herrmann H, Sison EA, Magoon D, Qi J, Blatt K, Wunderlich M et al (2011) RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 478:524
  • PAC-0877-21025-GP-supple 2-Table 1.xlsx
    PAC-0877-21025-GP-supple 1.xlsx
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索


    Article Metrics

    Article views (1041) PDF downloads(177) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint