Epigenetic modifications represent mechanisms by which cells may effectively translate multiple signaling inputs into phenotypic outputs. Recent research is revealing that redox metabolism is an increasingly important determinant of epigenetic control that may have significant ramifications in both human health and disease. Numerous characterized epigenetic marks, including histone methylation, acetylation, and ADP-ribosylation, as well as DNA methylation, have direct linkages to central metabolism through critical redox intermediates such as NAD+, S-adenosyl methionine, and 2-oxoglutarate. Fluctuations in these intermediates caused by both normal and pathologic stimuli may thus have direct effects on epigenetic signaling that lead to measurable changes in gene expression. In this comprehensive review, we present surveys of both metabolism-sensitive epigenetic enzymes and the metabolic processes that may play a role in their regulation. To close, we provide a series of clinically relevant illustrations of the communication between metabolism and epigenetics in the pathogenesis of cardiovascular disease, Alzheimer disease, cancer, and environmental toxicity. We anticipate that the regulatory mechanisms described herein will play an increasingly large role in our understanding of human health and disease as epigenetics research progresses. Antioxid. Redox Signal. 15, 551–589.
AndersonRM, BittermanKJ, WoodJG, MedvedikO, CohenH, LinSS, ManchesterJK, GordonJI, SinclairDA. Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels. J Biol Chem, 277:18881–18890. 2002.
7.
AnekondaTS, ReddyPH. Neuronal protection by sirtuins in Alzheimer's disease. J Neurochem, 96:305–313. 2006.
8.
AnzilottiC, PratesiF, TommasiC, MiglioriniP. Peptidylarginine deiminase 4 and citrullination in health and disease. Autoimmun Rev, 9:158–160. 2010.
9.
AveryOT, MacleodCM, McCartyM. Studies on the chemical nature of the substance inducing transformation of pneumococcal types: induction of transformation by a desoxyribonucleic acid fraction isolated from pneumococcus type III. J Exp Med, 79:137–158. 1944.
10.
AvilaMA, BerasainC, TorresL, Martin-DuceA, CorralesFJ, YangH, PrietoJ, LuSC, CaballeriaJ, RodesJet al.Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma. J Hepatol, 33:907–914. 2000.
11.
AyoubN, NomaK, IsaacS, KahanT, GrewalSI, CohenA. A novel jmjC domain protein modulates heterochromatization in fission yeast. Mol Cell Biol, 23:4356–4370. 2003.
12.
BarakAJ, BeckenhauerHC, TumaDJ. Methionine synthase. a possible prime site of the ethanolic lesion in liver. Alcohol, 26:65–67. 2002.
13.
Berchner-PfannschmidtU, TugS, KirschM, FandreyJ. Oxygen-sensing under the influence of nitric oxide. Cell Signal, 22:349–356. 2010.
BergerSJ, SudarDC, BergerNA. Metabolic consequences of DNA damage: DNA damage induces alterations in glucose metabolism by activation of poly (ADP-ribose) polymerase. Biochem Biophys Res Commun, 134:227–232. 1986.
16.
BestorTH. The DNA methyltransferases of mammals. Hum Mol Genet, 9:2395–2402. 2000.
17.
BilsboroughJ, Van PelA, UyttenhoveC, BoonT, Van den EyndeBJ. Identification of a second major tumor-specific antigen recognized by CTLs on mouse mastocytoma P815. J Immunol, 162:3534–3540. 1999.
18.
BirdA. Perceptions of epigenetics. Nature, 447:396–398. 2007.
19.
BittermanKJ, AndersonRM, CohenHY, Latorre-EstevesM, SinclairDA. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J Biol Chem, 277:45099–45107. 2002.
20.
BogdanovicO, VeenstraGJ. DNA methylation and methyl-CpG binding proteins: developmental requirements and function. Chromosoma, 118:549–565. 2009.
21.
BohmL, SchneeweissFA, SharanRN, FeinendegenLE. Influence of histone acetylation on the modification of cytoplasmic and nuclear proteins by ADP-ribosylation in response to free radicals. Biochim Biophys Acta, 1334:149–154. 1997.
22.
BrahmachariHD, JosephS. Cobalt compounds for the control of hypoxic stress. Aerosp Med, 44:636–638. 1973.
23.
BrickellKL, LeverenzJB, SteinbartEJ, RumbaughM, SchellenbergGD, NochlinD, LampeTH, HolmIE, Van DeerlinV, YuanWet al.Clinicopathological concordance and discordance in three monozygotic twin pairs with familial Alzheimer's disease. J Neurol Neurosurg Psychiatry, 78:1050–1055. 2007.
24.
BrodayL, PengW, KuoMH, SalnikowK, ZorodduM, CostaM. Nickel compounds are novel inhibitors of histone H4 acetylation. Cancer Res, 60:238–241. 2000.
25.
BrunengraberH. Alpha-ketoglutarate is the precursor of L-2-hydroxyglutarate. J Inherit Metab Dis, 30:628. 2007.
26.
BrunengraberH, RoeCR. Anaplerotic molecules: current and future. J Inherit Metab Dis, 29:327–331. 2006.
27.
BubberP, HaroutunianV, FischG, BlassJP, GibsonGE. Mitochondrial abnormalities in Alzheimer brain: mechanistic implications. Ann Neurol, 57:695–703. 2005.
CallapinaM, ZhouJ, SchnitzerS, MetzenE, LohrC, DeitmerJW, BruneB. Nitric oxide reverses desferrioxamine- and hypoxia-evoked HIF-1alpha accumulation—implications for prolyl hydroxylase activity and iron. Exp Cell Res, 306:274–284. 2005.
31.
CampaneroMR, ArmstrongMI, FlemingtonEK. CpG methylation as a mechanism for the regulation of E2F activity. Proc Natl Acad Sci U S A, 97:6481–6486. 2000.
32.
CaoD, TalTL, GravesLM, GilmourI, LinakW, ReedW, BrombergPA, SametJM. Diesel exhaust particulate-induced activation of Stat3 requires activities of EGFR and Src in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol, 292:L422–L429. 2007.
33.
CardosoSM, SantosS, SwerdlowRH, OliveiraCR. Functional mitochondria are required for amyloid beta-mediated neurotoxicity. FASEB J, 15:1439–1441. 2001.
34.
CastroL, RodriguezM, RadiR. Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide. J Biol Chem, 269:29409–29415. 1994.
35.
CastroR, RiveraI, StruysEA, JansenEE, RavascoP, CamiloME, BlomHJ, JakobsC, Tavares de AlmeidaI. Increased homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease. Clin Chem, 49:1292–1296. 2003.
36.
CederbaumAI. Hepatoprotective effects of S-adenosyl-L-methionine against alcohol- and cytochrome P450 2E1-induced liver injury. World J Gastroenterol, 16:1366–1376. 2010.
37.
CerveraAM, BayleyJP, DevileeP, McCreathKJ. Inhibition of succinate dehydrogenase dysregulates histone modification in mammalian cells. Mol Cancer, 8. 2009.
38.
ChambonP, WeillJD, MandelP. Nicotinamide mononucleotide activation of new DNA-dependent polyadenylic acid synthesizing nuclear enzyme. Biochem Biophys Res Commun, 11:39–43. 1963.
39.
ChangB, ChenY, ZhaoY, BruickRK. JMJD6 is a histone arginine demethylase. Science, 318:444–447. 2007.
40.
ChangX, FangK. PADI4 and tumourigenesis. Cancer Cell Int, 10:7. 2010.
ChenQ, EspeyMG, SunAY, LeeJH, KrishnaMC, ShacterE, ChoykePL, PooputC, KirkKL, BuettnerGRet al.Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci U S A, 104:8749–8754. 2007.
43.
ChenQ, EspeyMG, SunAY, PooputC, KirkKL, KrishnaMC, KhoshDB, DriskoJ, LevineM. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci U S A, 105:11105–11109. 2008.
44.
ChenZ, LiY, ZhangH, HuangP, LuthraR. Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene, 29:4362–4368. 2010.
45.
ChengY, LiuX, ZhangS, LinY, YangJ, ZhangC. MicroRNA-21 protects against the H(2)O(2)-induced injury on cardiac myocytes via its target gene PDCD4. J Mol Cell Cardiol, 47:5–14. 2009.
46.
ChouliarasL, RuttenBP, KenisG, PeerboomsO, VisserPJ, VerheyF, vanOs J, SteinbuschHW, van den HoveDL. Epigenetic regulation in the pathophysiology of Alzheimer's disease. Prog Neurobiol, 90:498–510. 2010.
47.
CostaFF. Non-coding RNAs, epigenetics and complexity. Gene, 410:9–17. 2008.
48.
CostaM, DavidsonTL, ChenH, KeQ, ZhangP, YanY, HuangC, KluzT. Nickel carcinogenesis: epigenetics and hypoxia signaling. Mutat Res, 592:79–88. 2005.
49.
CoutureJF, CollazoE, Ortiz-TelloPA, BrunzelleJS, TrievelRC. Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase. Nat Struct Mol Biol, 14:689–695. 2007.
50.
CozziA, CorsiB, LeviS, SantambrogioP, AlbertiniA, ArosioP. Overexpression of wild type and mutated human ferritin H-chain in HeLa cells: in vivo role of ferritin ferroxidase activity. J Biol Chem, 275:25122–25129. 2000.
51.
CullenJJ. Ascorbate induces autophagy in pancreatic cancer. Autophagy, 6:421–422. 2010.
DantzerF, de La RubiaG, Menissier-De MurciaJ, HostomskyZ, de MurciaG, SchreiberV. Base excision repair is impaired in mammalian cells lacking Poly(ADP-ribose) polymerase-1. Biochemistry, 39:7559–7569. 2000.
55.
de CapoaA, FebboFR, GiovannelliF, NiveleauA, ZardoG, MarenziS, CaiafaP. Reduced levels of poly(ADP-ribosyl)ation result in chromatin compaction and hypermethylation as shown by cell-by-cell computer-assisted quantitative analysis. FASEB J, 13:89–93. 1999.
56.
De LucaA, SacchettaP, NiedduM, Di IlioC, FavaloroB. Important roles of multiple Sp1 binding sites and epigenetic modifications in the regulation of the methionine sulfoxide reductase B1 (MsrB1) promoter. BMC Mol Biol, 8:39. 2007.
57.
de MurciaG, HuletskyA, LamarreD, GaudreauA, PouyetJ, DauneM, PoirierGG. Modulation of chromatin superstructure induced by poly(ADP-ribose) synthesis and degradation. J Biol Chem, 261:7011–7017. 1986.
58.
DenkoNC. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer, 8:705–713. 2008.
59.
DeubzerB, MayerF, KuciZ, NiewischM, MerkelG, HandgretingerR, BrucheltG. H(2)O(2)-mediated cytotoxicity of pharmacologic ascorbate concentrations to neuroblastoma cells: potential role of lactate and ferritin. Cell Physiol Biochem, 25:767–774. 2010.
60.
Di PietroG, MagnoLA, Rios-SantosF. Glutathione S-transferases: an overview in cancer research. Expert Opin Drug Metab Toxicol, 6:153–170. 2010.
61.
DillonSC, ZhangX, TrievelRC, ChengX. The SET-domain protein superfamily: protein lysine methyltransferases. Genome Biol, 6:227. 2005.
62.
Dje N'GuessanP, RiedigerF, VardarovaK, ScharfS, EitelJ, OpitzB, SlevogtH, WeichertW, HockeAC, SchmeckBet al.Statins control oxidized LDL-mediated histone modifications and gene expression in cultured human endothelial cells. Arterioscler Thromb Vasc Biol, 29:380–386. 2009.
63.
DomannFE, RiceJC, HendrixMJ, FutscherBW. Epigenetic silencing of maspin gene expression in human breast cancers. Int J Cancer, 85:805–810. 2000.
64.
DonaldSP, SunXY, HuCA, YuJ, MeiJM, ValleD, PhangJM. Proline oxidase, encoded by p53-induced gene-6, catalyzes the generation of proline-dependent reactive oxygen species. Cancer Res, 61:1810–1815. 2001.
65.
DoyleK, FitzpatrickFA. Redox signaling, alkylation (carbonylation) of conserved cysteines inactivates class I histone deacetylases 1, 2, and 3 and antagonizes their transcriptional repressor function. J Biol Chem, 285:17417–17424. 2010.
66.
DuceAM, OrtizP, CabreroC, MatoJM. S-adenosyl-L-methionine synthetase and phospholipid methyltransferase are inhibited in human cirrhosis. Hepatology, 8:65–68. 1988.
67.
DuncanT, TrewickSC, KoivistoP, BatesPA, LindahlT, SedgwickB. Reversal of DNA alkylation damage by two human dioxygenases. Proc Natl Acad Sci U S A, 99:16660–16665. 2002.
68.
EckerJR, DavisRW. Inhibition of gene expression in plant cells by expression of antisense RNA. Proc Natl Acad Sci U S A, 83:5372–5376. 1986.
69.
El RamyR, MagrounN, MessadecqN, GauthierLR, BoussinFD, Kolthur-SeetharamU, SchreiberV, McBurneyMW, Sassone-CorsiP, DantzerF. Functional interplay between Parp-1 and SirT1 in genome integrity and chromatin-based processes. Cell Mol Life Sci, 66:3219–3234. 2009.
70.
EstiuG, WestN, MazitschekR, GreenbergE, BradnerJE, WiestO. On the inhibition of histone deacetylase 8. Bioorg Med Chem, 18:4103–4110. 2010.
71.
FalnesPO, JohansenRF, SeebergE. AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli. Nature, 419:178–182. 2002.
72.
FavaroE, RamachandranA, McCormickR, GeeH, BlancherC, CrosbyM, DevlinC, BlickC, BuffaF, LiJLet al.MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU. PLoS ONE, 5:e10345. 2010.
73.
FavierJ, BriereJJ, BurnichonN, RiviereJ, VescovoL, BenitP, Giscos-DouriezI, De ReyniesA, BertheratJ, BadoualCet al.The Warburg effect is genetically determined in inherited pheochromocytomas. PLoS ONE, 4:e7094. 2009.
74.
FeinbergAP, OhlssonR, HenikoffS. The epigenetic progenitor origin of human cancer. Nat Rev Genet, 7:21–33. 2006.
75.
Fernandez-ChecaJC, ColellA, Garcia-RuizC. S-Adenosyl-L-methionine and mitochondrial reduced glutathione depletion in alcoholic liver disease. Alcohol, 27:179–183. 2002.
76.
FinstererJ. Leigh and Leigh-like syndrome in children and adults. Pediatr Neurol, 39:223–235. 2008.
77.
FlashmanE, DaviesSL, YeohKK, SchofieldCJ. Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. Biochem J, 427:135–142. 2010.
78.
FlintDH, TuminelloJF, EmptageMH. The inactivation of Fe-S cluster containing hydro-lyases by superoxide. J Biol Chem, 268:22369–22376. 1993.
79.
FornerisF, BattaglioliE, MatteviA, BindaC. New roles of flavoproteins in molecular cell biology: histone demethylase LSD1 and chromatin. FEBS J, 276:4304–4312. 2009.
80.
FornerisF, BindaC, VanoniMA, MatteviA, BattaglioliE. Histone demethylation catalysed by LSD1 is a flavin-dependent oxidative process. FEBS Lett, 579:2203–2207. 2005.
81.
FriedmanJM, LiangG, LiuCC, WolffEM, TsaiYC, YeW, ZhouX, JonesPA. The putative tumor suppressor microRNA-101 modulates the cancer epigenome by repressing the polycomb group protein EZH2. Cancer Res, 69:2623–2629. 2009.
82.
FryI. The Role of natural selection in the origin of life. Orig Life Evol Biosph, 41:3–16. 2011.
83.
FryeRA. Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. Biochem Biophys Res Commun, 260:273–279. 1999.
84.
FujitaN, WatanabeS, IchimuraT, TsuruzoeS, ShinkaiY, TachibanaM, ChibaT, NakaoM. Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression. J Biol Chem, 278:24132–24138. 2003.
85.
FuksF, HurdPJ, DeplusR, KouzaridesT. The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res, 31:2305–2312. 2003.
86.
FutscherBW, O'MearaMM, KimCJ, RennelsMA, LuD, GrumanLM, SeftorRE, HendrixMJ, DomannFE. Aberrant methylation of the maspin promoter is an early event in human breast cancer. Neoplasia, 6:380–389. 2004.
87.
GanttSL, GattisSG, FierkeCA. Catalytic activity and inhibition of human histone deacetylase 8 is dependent on the identity of the active site metal ion. Biochemistry, 45:6170–6178. 2006.
GardnerPR, FridovichI. Superoxide sensitivity of the Escherichia coli aconitase. J Biol Chem, 266:19328–19333. 1991.
90.
GardnerPR, RaineriI, EpsteinLB, WhiteCW. Superoxide radical and iron modulate aconitase activity in mammalian cells. J Biol Chem, 270:13399–13405. 1995.
91.
GatzM, FratiglioniL, JohanssonB, BergS, MortimerJA, ReynoldsCA, FiskeA, PedersenNL. Complete ascertainment of dementia in the Swedish Twin Registry: the HARMONY study. Neurobiol Aging, 26:439–447. 2005.
92.
GatzM, MortimerJA, FratiglioniL, JohanssonB, BergS, ReynoldsCA, PedersenNL. Potentially modifiable risk factors for dementia in identical twins. Alzheimers Dement, 2:110–117. 2006.
93.
GatzM, ReynoldsCA, FratiglioniL, JohanssonB, MortimerJA, BergS, FiskeA, PedersenNL. Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry, 63:168–174. 2006.
94.
Gimenez-RoqueploAP, FavierJ, RustinP, MouradJJ, PlouinPF, CorvolP, RotigA, JeunemaitreX. The R22 × mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway. Am J Hum Genet, 69:1186–1197. 2001.
95.
Gimenez-RoqueploAP, FavierJ, RustinP, RieublandC, CrespinM, NauV, Khau Van KienP, CorvolP, PlouinPF, JeunemaitreX. Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas. Cancer Res, 63:5615–5621. 2003.
96.
GoldererG, GrobnerP. ADP-ribosylation of core histones and their acetylated subspecies. Biochem J, 277,Pt 3:607–610. 1991.
97.
GrantS. Targeting histone demethylases in cancer therapy. Clin Cancer Res, 15:7111–7113. 2009.
98.
GreenA, BeerP. Somatic mutations of IDH1 and IDH2 in the leukemic transformation of myeloproliferative neoplasms. N Engl J Med, 362:369–370. 2010.
99.
GreenKN, SteffanJS, Martinez-CoriaH, SunX, SchreiberSS, ThompsonLM, LaFerlaFM. Nicotinamide restores cognition in Alzheimer's disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau. J Neurosci, 28:11500–11510. 2008.
100.
GregorettiIV, LeeYM, GoodsonHV. Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J Mol Biol, 338:17–31. 2004.
101.
GrewalSI. RNAi-dependent formation of heterochromatin and its diverse functions. Curr Opin Genet Dev, 20:134–141. 2010.
102.
GrossS, CairnsRA, MindenMD, DriggersEM, BittingerMA, JangHG, SasakiM, JinS, SchenkeinDP, SuSMet al.Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med, 207:339–344. 2010.
103.
GuarenteL. Calorie restriction and SIR2 genes—towards a mechanism. Mech Ageing Dev, 126:923–928. 2005.
104.
HaigisMC, GuarenteLP. Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction. Genes Dev, 20:2913–2921. 2006.
105.
HajkovaP, JeffriesSJ, LeeC, MillerN, JacksonSP, SuraniMA. Genome-wide reprogramming in the mouse germ line entails the base excision repair pathway. Science, 329:78–82. 2010.
106.
HakmeA, WongHK, DantzerF, SchreiberV. The expanding field of poly(ADP-ribosyl)ation reactions. “Protein modifications: beyond the usual suspects” Review Series. EMBO Rep, 9:1094–1100. 2008.
107.
HalilogluG, JobardF, OguzKK, AnlarB, AkalanN, CoskunT, SassJO, FischerJ, TopcuM. L-2-hydroxyglutaric aciduria and brain tumors in children with mutations in the L2HGDH gene: neuroimaging findings. Neuropediatrics, 39:119–122. 2008.
HaoHX, KhalimonchukO, SchradersM, DephoureN, BayleyJP, KunstH, DevileeP, CremersCW, SchiffmanJD, BentzBGet al.SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science, 325:1139–1142. 2009.
110.
HassaPO, HaenniSS, ElserM, HottigerMO. Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going?Microbiol Mol Biol Rev, 70:789–829. 2006.
111.
HassaPO, HottigerMO. The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases. Front Biosci, 13:3046–3082. 2008.
112.
HausladenA, FridovichI. Superoxide and peroxynitrite inactivate aconitases, but nitric oxide does not. J Biol Chem, 269:29405–29408. 1994.
113.
HawkinsPG, SantosoS, AdamsC, AnestV, MorrisKV. Promoter targeted small RNAs induce long-term transcriptional gene silencing in human cells. Nucleic Acids Res, 37:2984–2995. 2009.
114.
HedigerMA. New view at C. Nat Med, 8:445–446. 2002.
115.
HeintzmanND, HonGC, HawkinsRD, KheradpourP, StarkA, HarpLF, YeZ, LeeLK, StuartRK, ChingCWet al.Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature, 459:108–112. 2009.
116.
HewitsonKS, McNeillLA, RiordanMV, TianYM, BullockAN, WelfordRW, ElkinsJM, OldhamNJ, BhattacharyaS, GleadleJMet al.Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. J Biol Chem, 277:26351–26355. 2002.
117.
HipkissAR. Energy metabolism, altered proteins, sirtuins and ageing: converging mechanisms?Biogerontology, 9:49–55. 2008.
HirsilaM, KoivunenP, GunzlerV, KivirikkoKI, MyllyharjuJ. Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor. J Biol Chem, 278:30772–30780. 2003.
120.
HitchlerMJ, DomannFE. An epigenetic perspective on the free radical theory of development. Free Radic Biol Med, 43:1023–1036. 2007.
121.
HitchlerMJ, DomannFE. Metabolic defects provide a spark for the epigenetic switch in cancer. Free Radic Biol Med, 47:115–127. 2009.
122.
HitchlerMJ, WikainapakulK, YuL, PowersK, AttatippaholkunW, DomannFE. Epigenetic regulation of manganese superoxide dismutase expression in human breast cancer cells. Epigenetics, 1:163–171. 2006.
123.
HollidayR. The inheritance of epigenetic defects. Science, 238:163–170. 1987.
124.
HuangY, MyersSJ, DingledineR. Transcriptional repression by REST: recruitment of Sin3A and histone deacetylase to neuronal genes. Nat Neurosci, 2:867–872. 1999.
125.
HubbertC, GuardiolaA, ShaoR, KawaguchiY, ItoA, NixonA, YoshidaM, WangXF, YaoTP. HDAC6 is a microtubule-associated deacetylase. Nature, 417:455–458. 2002.
126.
HyunDH, HernandezJO, MattsonMP, de CaboR. The plasma membrane redox system in aging. Ageing Res Rev, 5:209–220. 2006.
127.
Iguchi-ArigaSM, SchaffnerW. CpG methylation of the cAMP-responsive enhancer/promoter sequence TGACGTCA abolishes specific factor binding as well as transcriptional activation. Genes Dev, 3:612–619. 1989.
128.
IllingworthRS, BirdAP. CpG islands—“a rough guide.”FEBS Lett, 583:1713–1720. 2009.
129.
ImaiS, ArmstrongCM, KaeberleinM, GuarenteL. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature, 403:795–800. 2000.
130.
IngrossoD, PernaAF. Epigenetics in hyperhomocysteinemic states. A special focus on uremia. Biochim Biophys Acta, 1790:892–899. 2009.
131.
IsaacsJS, JungYJ, MoleDR, LeeS, Torres-CabalaC, ChungYL, MerinoM, TrepelJ, ZbarB, ToroJet al.HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell, 8:143–153. 2005.
132.
ItoK, HanazawaT, TomitaK, BarnesPJ, AdcockIM. Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration. Biochem Biophys Res Commun, 315:240–245. 2004.
133.
JamesLP, MayeuxPR, HinsonJA. Acetaminophen-induced hepatotoxicity. Drug Metab Dispos, 31:1499–1506. 2003.
134.
JeltschA. On the enzymatic properties of Dnmt1: specificity, processivity, mechanism of linear diffusion and allosteric regulation of the enzyme. Epigenetics, 1:63–66. 2006.
135.
JeningaEH, SchoonjansK, AuwerxJ. Reversible acetylation of PGC-1: connecting energy sensors and effectors to guarantee metabolic flexibility. Oncogene, 29:4617–4624. 2010.
136.
JensenTJ, NovakP, WnekSM, GandolfiAJ, FutscherBW. Arsenicals produce stable progressive changes in DNA methylation patterns that are linked to malignant transformation of immortalized urothelial cells. Toxicol Appl Pharmacol, 241:221–229. 2009.
JenuweinT, AllisCD. Translating the histone code. Science, 293:1074–1080. 2001.
139.
JenuweinT, LaibleG, DornR, ReuterG. SET domain proteins modulate chromatin domains in eu- and heterochromatin. Cell Mol Life Sci, 54:80–93. 1998.
140.
JonesJE, CauseyCP, KnuckleyB, Slack-NoyesJL, ThompsonPR. Protein arginine deiminase 4 (PAD4): current understanding and future therapeutic potential. Curr Opin Drug Discov Devel, 12:616–627. 2009.
141.
JulienC, TremblayC, EmondV, LebbadiM, SalemN.Jr, BennettDA, CalonF. Sirtuin 1 reduction parallels the accumulation of tau in Alzheimer disease. J Neuropathol Exp Neurol, 68:48–58. 2009.
142.
KawaguchiY, KovacsJJ, McLaurinA, VanceJM, ItoA, YaoTP. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell, 115:727–738. 2003.
143.
KawaiK, LiYS, SongMF, KasaiH. DNA methylation by dimethyl sulfoxide and methionine sulfoxide triggered by hydroxyl radical and implications for epigenetic modifications. Bioorg Med Chem Lett, 20:260–265. 2010.
144.
KharbandaKK. Role of transmethylation reactions in alcoholic liver disease. World J Gastroenterol, 13:4947–4954. 2007.
145.
KimD, NguyenMD, DobbinMM, FischerA, SananbenesiF, RodgersJT, DelalleI, BaurJA, SuiG, ArmourSMet al.SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. EMBO J, 26:3169–3179. 2007.
146.
KimJS, ShuklaSD. Histone h3 modifications in rat hepatic stellate cells by ethanol. Alcohol Alcohol, 40:367–372. 2005.
147.
KimJS, ShuklaSD. Acute in vivo effect of ethanol (binge drinking) on histone H3 modifications in rat tissues. Alcohol Alcohol, 41:126–132. 2006.
148.
KingA, SelakMA, GottliebE. Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene, 25:4675–4682. 2006.
149.
KirklandJB. Niacin status impacts chromatin structure. J Nutr, 139:2397–2401. 2009.
150.
KnowlesHJ, RavalRR, HarrisAL, RatcliffePJ. Effect of ascorbate on the activity of hypoxia-inducible factor in cancer cells. Cancer Res, 63:1764–1768. 2003.
151.
Kolthur-SeetharamU, DantzerF, McBurneyMW, de MurciaG, Sassone-CorsiP. Control of AIF-mediated cell death by the functional interplay of SIRT1 and PARP-1 in response to DNA damage. Cell Cycle, 5:873–877. 2006.
152.
KomotarRJ, StarkeRM, SistiMB, ConnollyES. IDH1 and IDH2 mutations in gliomas and the associated induction of hypoxia-inducible factor and production of 2-hydroxyglutarate. Neurosurgery, 66:N20–N21. 2010.
153.
KonijnAM, GlicksteinH, VaismanB, Meyron-HoltzEG, SlotkiIN, CabantchikZI. The cellular labile iron pool and intracellular ferritin in K562 cells. Blood, 94:2128–2134. 1999.
154.
KouzaridesT. Chromatin modifications and their function. Cell, 128:693–705. 2007.
KuoMH, AllisCD. Roles of histone acetyltransferases and deacetylases in gene regulation. Bioessays, 20:615–626. 1998.
161.
KuttyRK, SamuelW, JaworskiC, DuncanT, NagineniCN, RaghavachariN, WiggertB, RedmondTM. MicroRNA expression in human retinal pigment epithelial (ARPE-19) cells: increased expression of microRNA-9 by N-(4-hydroxyphenyl)retinamide. Mol Vis, 16:1475–1486. 2010.
162.
LachnerM, O'CarrollD, ReaS, MechtlerK, JenuweinT. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature, 410:116–120. 2001.
163.
LalG, PadmanabhaL, ProvenzanoM, FitzgeraldM, WeydertJ, DomannFE. Regulation of 14-3-3 sigma expression in human thyroid carcinoma is epigenetically regulated by aberrant cytosine methylation. Cancer Lett, 267:165–174. 2008.
164.
LanderES, LintonLM, BirrenB, NusbaumC, ZodyMC, BaldwinJ, DevonK, DewarK, DoyleM, FitzHughWet al.Initial sequencing and analysis of the human genome. Nature, 409:860–921. 2001.
165.
LandryJ, SlamaJT, SternglanzR. Role of NAD(+) in the deacetylase activity of the SIR2-like proteins. Biochem Biophys Res Commun, 278:685–690. 2000.
166.
LandryJ, SuttonA, TafrovST, HellerRC, StebbinsJ, PillusL, SternglanzR. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc Natl Acad Sci U S A, 97:5807–5811. 2000.
167.
LatiniA, da SilvaCG, FerreiraGC, SchuckPF, ScussiatoK, SarkisJJ, Dutra FilhoCS, WyseAT, WannmacherCM, WajnerM. Mitochondrial energy metabolism is markedly impaired by D-2-hydroxyglutaric acid in rat tissues. Mol Genet Metab, 86:188–199. 2005.
168.
LatiniA, ScussiatoK, RosaRB, LeipnitzG, LlesuyS, Bello-KleinA, Dutra-FilhoCS, WajnerM. Induction of oxidative stress by L-2-hydroxyglutaric acid in rat brain. J Neurosci Res, 74:103–110. 2003.
169.
LatiniA, ScussiatoK, RosaRB, LlesuyS, Bello-KleinA, Dutra-FilhoCS, WajnerM. D-2-hydroxyglutaric acid induces oxidative stress in cerebral cortex of young rats. Eur J Neurosci, 17:2017–2022. 2003.
170.
LawlessMW, NorrisS, O'ByrneKJ, GraySG. Targeting histone deacetylases for the treatment of disease. J Cell Mol Med, 13:826–852. 2009.
171.
LeeBC, DikiyA, KimHY, GladyshevVN. Functions and evolution of selenoprotein methionine sulfoxide reductases. Biochim Biophys Acta, 1790:1471–1477. 2009.
172.
LeebM, SteffenPA, WutzA. X chromosome inactivation sparked by non-coding RNAs. RNA Biol, 6:94–99. 2009.
173.
LeiKF, WangYF, ZhuXQ, LuPC, SunBS, JiaHL, RenN, YeQH, SunHC, WangLet al.Identification of MSRA gene on chromosome 8p as a candidate metastasis suppressor for human hepatitis B virus-positive hepatocellular carcinoma. BMC Cancer, 7:172. 2007.
174.
LertratanangkoonK, OrkiszewskiRS, ScimecaJM. Methyl-donor deficiency due to chemically induced glutathione depletion. Cancer Res, 56:995–1005. 1996.
175.
LertratanangkoonK, SavarajN, ScimecaJM, ThomasML. Glutathione depletion-induced thymidylate insufficiency for DNA repair synthesis. Biochem Biophys Res Commun, 234:470–475. 1997.
176.
LertratanangkoonK, WuCJ, SavarajN, ThomasML. Alterations of DNA methylation by glutathione depletion. Cancer Lett, 120:149–156. 1997.
177.
LevineM, EspeyMG, ChenQ. Losing and finding a way at C: new promise for pharmacologic ascorbate in cancer treatment. Free Radic Biol Med, 47:27–29. 2009.
178.
LiQ, KeQ, CostaM. Alterations of histone modifications by cobalt compounds. Carcinogenesis, 30:1243–1251. 2009.
179.
LiangG, LinJC, WeiV, YooC, ChengJC, NguyenCT, WeisenbergerDJ, EggerG, TakaiD, GonzalesFAet al.Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome. Proc Natl Acad Sci U S A, 101:7357–7362. 2004.
180.
LinSJ, DefossezPA, GuarenteL. Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science, 289:2126–2128. 2000.
181.
LinSJ, GuarenteL. Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease. Curr Opin Cell Biol, 15:241–246. 2003.
LinY, LiuX, ChengY, YangJ, HuoY, ZhangC. Involvement of MicroRNAs in hydrogen peroxide-mediated gene regulation and cellular injury response in vascular smooth muscle cells. J Biol Chem, 284:7903–7913. 2009.
184.
LiuH, HuQ, D'ErcoleAJ, YeP. Histone deacetylase 11 regulates oligodendrocyte-specific gene expression and cell development in OL-1 oligodendroglia cells. Glia, 57:1–12. 2009.
185.
LiuW, ZabirnykO, WangH, ShiaoYH, NickersonML, KhalilS, AndersonLM, PerantoniAO, PhangJM. miR-23b* targets proline oxidase, a novel tumor suppressor protein in renal cancer. Oncogene, 29:4914–4924. 2010.
186.
LiuY, BorchertGL, DonaldSP, SurazynskiA, HuCA, WeydertCJ, OberleyLW, PhangJM. MnSOD inhibits proline oxidase-induced apoptosis in colorectal cancer cells. Carcinogenesis, 26:1335–1342. 2005.
187.
LiuY, BorchertGL, SurazynskiA, PhangJM. Proline oxidase, a p53-induced gene, targets COX-2/PGE2 signaling to induce apoptosis and inhibit tumor growth in colorectal cancers. Oncogene, 27:6729–6737. 2008.
188.
LuSC. Regulation of hepatic glutathione synthesis: current concepts and controversies. FASEB J, 13:1169–1183. 1999.
189.
LuSC. Regulation of glutathione synthesis. Mol Aspects Med, 30:42–59. 2009.
190.
LukiwWJ, PogueAI. Induction of specific micro RNA (miRNA) species by ROS-generating metal sulfates in primary human brain cells. J Inorg Biochem, 101:1265–1269. 2007.
MalecovaB, MorrisKV. Transcriptional gene silencing through epigenetic changes mediated by non-coding RNAs. Curr Opin Mol Ther, 12:214–222. 2010.
193.
MarcucciG, MaharryK, WuYZ, RadmacherMD, MrozekK, MargesonD, HollandKB, WhitmanSP, BeckerH, SchwindSet al.IDH1 and IDH2 gene mutations identify novel molecular subsets within De Novo cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study. J Clin Oncol, 28:2348–2355. 2010.
MartinM, KettmannR, DequiedtF. Class IIa histone deacetylases: regulating the regulators. Oncogene, 26:5450–5467. 2007.
196.
MastroeniD, McKeeA, GroverA, RogersJ, ColemanPD. Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer's disease. PLoS ONE, 4:e6617. 2009.
197.
MaunakeaAK, NagarajanRP, BilenkyM, BallingerTJ, D'SouzaC, FouseSD, JohnsonBE, HongC, NielsenC, ZhaoYet al.Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature, 466:253–257. 2010.
198.
MaxwellP, SalnikowK. HIF-1: an oxygen and metal responsive transcription factor. Cancer Biol Ther, 3:29–35. 2004.
199.
MaxwellSA, KochevarGJ. Identification of a p53-response element in the promoter of the proline oxidase gene. Biochem Biophys Res Commun, 369:308–313. 2008.
200.
McNeillLA, FlashmanE, BuckMR, HewitsonKS, CliftonIJ, JeschkeG, ClaridgeTD, EhrismannD, OldhamNJ, SchofieldCJ. Hypoxia-inducible factor prolyl hydroxylase 2 has a high affinity for ferrous iron and 2-oxoglutarate. Mol Biosyst, 1:321–324. 2005.
201.
MeisterA. Glutathione metabolism and its selective modification. J Biol Chem, 263:17205–17208. 1988.
202.
MeisterA, AndersonME. Glutathione. Annu Rev Biochem, 52:711–760. 1983.
MetzenE, ZhouJ, JelkmannW, FandreyJ, BruneB. Nitric oxide impairs normoxic degradation of HIF-1alpha by inhibition of prolyl hydroxylases. Mol Biol Cell, 14:3470–3481. 2003.
205.
Meyron-HoltzEG, VaismanB, CabantchikZI, FibachE, RouaultTA, HershkoC, KonijnAM. Regulation of intracellular iron metabolism in human erythroid precursors by internalized extracellular ferritin. Blood, 94:3205–3211. 1999.
206.
MikirovaNA, CasciariJJ, RiordanNH. Ascorbate inhibition of angiogenesis in aortic rings ex vivo and subcutaneous Matrigel plugs in vivo. J Angiogenes Res, 2:2. 2010.
207.
MillerG. Epigenetics. The seductive allure of behavioral epigenetics. Science, 329:24–27. 2010.
208.
MitroN, GodioC, De FabianiE, ScottiE, GalmozziA, GilardiF, CarusoD, Vigil ChaconAB, CrestaniM. Insights in the regulation of cholesterol 7alpha-hydroxylase gene reveal a target for modulating bile acid synthesis. Hepatology, 46:885–897. 2007.
209.
MonganPD, CapacchioneJ, WestS, KaraianJ, DuboisD, KeneallyR, SharmaP. Pyruvate improves redox status and decreases indicators of hepatic apoptosis during hemorrhagic shock in swine. Am J Physiol Heart Circ Physiol, 283:H1634–H1644. 2002.
210.
MoodieFM, MarwickJA, AndersonCS, SzulakowskiP, BiswasSK, BauterMR, KiltyI, RahmanI. Oxidative stress and cigarette smoke alter chromatin remodeling but differentially regulate NF-kappaB activation and proinflammatory cytokine release in alveolar epithelial cells. FASEB J, 18:1897–1899. 2004.
211.
MoreiraPI, ZhuX, WangX, LeeHG, NunomuraA, PetersenRB, PerryG, SmithMA. Mitochondria: a therapeutic target in neurodegeneration. Biochim Biophys Acta, 1802:212–220. 2010.
212.
MoreyL, HelinK. Polycomb group protein-mediated repression of transcription. Trends Biochem Sci, 35:323–332. 2010.
213.
MoroniI, BugianiM, D'IncertiL, MaccagnanoC, RimoldiM, BissolaL, PolloB, FinocchiaroG, UzielG. L-2-hydroxyglutaric aciduria and brain malignant tumors: a predisposing condition?Neurology, 62:1882–1884. 2004.
214.
MosammaparastN, ShiY. Reversal of histone methylation: biochemical and molecular mechanisms of histone demethylases. Annu Rev Biochem, 79:155–179. 2010.
215.
MuckenthalerMU, GalyB, HentzeMW. Systemic iron homeostasis and the iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory network. Annu Rev Nutr, 28:197–213. 2008.
216.
MuellerS. Iron regulatory protein 1 as a sensor of reactive oxygen species. Biofactors, 24:171–181. 2005.
217.
MurayamaA, OhmoriK, FujimuraA, MinamiH, Yasuzawa-TanakaK, KurodaT, OieS, DaitokuH, OkuwakiM, NagataKet al.Epigenetic control of rDNA loci in response to intracellular energy status. Cell, 133:627–639. 2008.
218.
NakayamaJ, RiceJC, StrahlBD, AllisCD, GrewalSI. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science, 292:110–113. 2001.
219.
NgSS, KavanaghKL, McDonoughMA, ButlerD, PilkaES, LienardBM, BrayJE, SavitskyP, GileadiO, von DelftFet al.Crystal structures of histone demethylase JMJD2A reveal basis for substrate specificity. Nature, 448:87–91. 2007.
220.
NunomuraA, PerryG, AlievG, HiraiK, TakedaA, BalrajEK, JonesPK, GhanbariH, WatayaT, ShimohamaSet al.Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol, 60:759–767. 2001.
NusinowDA, Hernandez-MunozI, FazzioTG, ShahGM, KrausWL, PanningB. Poly(ADP-ribose) polymerase 1 is inhibited by a histone H2A variant, MacroH2A, and contributes to silencing of the inactive X chromosome. J Biol Chem, 282:12851–12859. 2007.
223.
ObrosovaI, FallerA, BurganJ, OstrowE, WilliamsonJR. Glycolytic pathway, redox state of NAD(P)-couples and energy metabolism in lens in galactose-fed rats: effect of an aldose reductase inhibitor. Curr Eye Res, 16:34–43. 1997.
224.
ObrosovaIG, StevensMJ. Effect of dietary taurine supplementation on GSH and NAD(P)-redox status, lipid peroxidation, and energy metabolism in diabetic precataractous lens. Invest Ophthalmol Vis Sci, 40:680–688. 1999.
225.
OhnoS, OhnoY, SuzukiN, SomaG, InoueM. High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer. Anticancer Res, 29:809–815. 2009.
226.
OkarDA, ManzanoA, Navarro-SabateA, RieraL, BartronsR, LangeAJ. PFK-2/FBPase-2: maker and breaker of the essential biofactor fructose-2,6-bisphosphate. Trends Biochem Sci, 26:30–35. 2001.
227.
OoiSK, BestorTH. The colorful history of active DNA demethylation. Cell, 133:1145–1148. 2008.
OshiroMM, KimCJ, WozniakRJ, JunkDJ, Munoz-RodriguezJL, BurrJA, FitzgeraldM, PawarSC, CressAE, DomannFEet al.Epigenetic silencing of DSC3 is a common event in human breast cancer. Breast Cancer Res, 7:R669–R680. 2005.
230.
OtakeH, MiwaM, FujimuraS, SugimuraT. Binding of ADP-ribose polymer with histone. J Biochem, 65:145–146. 1969.
231.
OzdemirA, MasumotoH, FitzjohnP, VerreaultA, LogieC. Histone H3 lysine 56 acetylation: a new twist in the chromosome cycle. Cell Cycle, 5:2602–2608. 2006.
232.
OzerA, BruickRK. Non-heme dioxygenases: cellular sensors and regulators jelly rolled into one?Nat Chem Biol, 3:144–153. 2007.
233.
OzisikPA, AkalanN, PalaogluS, TopcuM. Medulloblastoma in a child with the metabolic disease L-2-hydroxyglutaric aciduria. Pediatr Neurosurg, 37:22–26. 2002.
234.
PaikWK, KimS. Enzymatic demethylation of calf thymus histones. Biochem Biophys Res Commun, 51:781–788. 1973.
235.
Pal-BhadraM, BhadraU, JacksonDE, MamathaL, ParkPH, ShuklaSD. Distinct methylation patterns in histone H3 at Lys-4 and Lys-9 correlate with up- & down-regulation of genes by ethanol in hepatocytes. Life Sci, 81:979–987. 2007.
236.
PanY, MansfieldKD, BertozziCC, RudenkoV, ChanDA, GiacciaAJ, SimonMC. Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro. Mol Cell Biol, 27:912–925. 2007.
237.
PandhareJ, CooperSK, PhangJM. Proline oxidase, a proapoptotic gene, is induced by troglitazone: evidence for both peroxisome proliferator-activated receptor gamma-dependent and -independent mechanisms. J Biol Chem, 281:2044–2052. 2006.
238.
PardananiA, LashoTL, FinkeCM, MaiM, McClureRF, TefferiA. IDH1 and IDH2 mutation analysis in chronic- and blast-phase myeloproliferative neoplasms. Leukemia, 24:1146–1151. 2010.
239.
ParkPH, MillerR, ShuklaSD. Acetylation of histone H3 at lysine 9 by ethanol in rat hepatocytes. Biochem Biophys Res Commun, 306:501–504. 2003.
240.
ParkPJ. ChIP-seq: advantages and challenges of a maturing technology. Nat Rev Genet, 10:669–680. 2009.
241.
PasiniB, StratakisCA. SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytoma-paraganglioma syndromes. J Intern Med, 266:19–42. 2009.
242.
PassosJF, SaretzkiG, AhmedS, NelsonG, RichterT, PetersH, WapplerI, BirketMJ, HaroldG, SchaeubleKet al.Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence. PLoS Biol, 5:e110. 2007.
243.
PassosJF, von ZglinickiT, SaretzkiG. Mitochondrial dysfunction and cell senescence: cause or consequence?Rejuvenation Res, 9:64–68. 2006.
244.
PearceLL, Martinez-BoschS, ManzanoEL, WinnicaDE, EpperlyMW, PetersonJ. The resistance of electron-transport chain Fe-S clusters to oxidative damage during the reaction of peroxynitrite with mitochondrial complex II and rat-heart pericardium. Nitric Oxide, 20:135–142. 2009.
245.
PetersAH, MermoudJE, O'CarrollD, PaganiM, SchweizerD, BrockdorffN, JenuweinT. Histone H3 lysine 9 methylation is an epigenetic imprint of facultative heterochromatin. Nat Genet, 30:77–80. 2002.
246.
PhangJM, DonaldSP, PandhareJ, LiuY. The metabolism of proline, a stress substrate, modulates carcinogenic pathways. Amino Acids, 35:681–690. 2008.
247.
PicardV, EpsztejnS, SantambrogioP, CabantchikZI, BeaumontC. Role of ferritin in the control of the labile iron pool in murine erythroleukemia cells. J Biol Chem, 273:15382–15386. 1998.
248.
PillaiJB, IsbatanA, ImaiS, GuptaMP. Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity. J Biol Chem, 280:43121–43130. 2005.
249.
PiperPW, HarrisNL, MacLeanM. Preadaptation to efficient respiratory maintenance is essential both for maximal longevity and the retention of replicative potential in chronologically ageing yeast. Mech Ageing Dev, 127:733–740. 2006.
250.
PourazarJ, MudwayIS, SametJM, HelledayR, BlombergA, WilsonSJ, FrewAJ, KellyFJ, SandstromT. Diesel exhaust activates redox-sensitive transcription factors and kinases in human airways. Am J Physiol Lung Cell Mol Physiol, 289:L724–L730. 2005.
251.
PowellCS, JacksonRM. Mitochondrial complex I, aconitase, and succinate dehydrogenase during hypoxia-reoxygenation: modulation of enzyme activities by MnSOD. Am J Physiol Lung Cell Mol Physiol, 285:L189–L198. 2003.
252.
QuenetD, El RamyR, SchreiberV, DantzerF. The role of poly(ADP-ribosyl)ation in epigenetic events. Int J Biochem Cell Biol, 41:60–65. 2009.
253.
RadtkeF, HugM, GeorgievO, MatsuoK, SchaffnerW. Differential sensitivity of zinc finger transcription factors MTF-1, Sp1 and Krox-20 to CpG methylation of their binding sites. Biol Chem Hoppe Seyler, 377:47–56. 1996.
254.
RamasamyR, TruebloodN, SchaeferS. Metabolic effects of aldose reductase inhibition during low-flow ischemia and reperfusion. Am J Physiol, 275,1 Pt 2:H195–H203. 1998.
255.
RichPR. The molecular machinery of Keilin's respiratory chain. Biochem Soc Trans, 31,Pt 6:1095–1105. 2003.
256.
RinnJL, KerteszM, WangJK, SquazzoSL, XuX, BrugmannSA, GoodnoughLH, HelmsJA, FarnhamPJ, SegalEet al.Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell, 129:1311–1323. 2007.
257.
RistoffE, LarssonA. Inborn errors in the metabolism of glutathione. Orphanet J Rare Dis, 2:16. 2007.
258.
RiveraA, MaxwellSA. The p53-induced gene-6 (proline oxidase) mediates apoptosis through a calcineurin-dependent pathway. J Biol Chem, 280:29346–29354. 2005.
259.
RothSY, DenuJM, AllisCD. Histone acetyltransferases. Annu Rev Biochem, 70:81–120. 2001.
RussellRR3rd, MommessinJI, TaegtmeyerH. Propionyl-L-carnitine-mediated improvement in contractile function of rat hearts oxidizing acetoacetate. Am J Physiol, 268,1 Pt 2:H441–H447. 1995.
263.
RussellRR3rd, TaegtmeyerH. Pyruvate carboxylation prevents the decline in contractile function of rat hearts oxidizing acetoacetate. Am J Physiol, 261,6 Pt 2:H1756–H1762. 1991.
264.
RzemR, Veiga-da-CunhaM, NoelG, GoffetteS, NassogneMC, TabarkiB, SchollerC, MarquardtT, VikkulaM, Van SchaftingenE. A gene encoding a putative FAD-dependent L-2-hydroxyglutarate dehydrogenase is mutated in L-2-hydroxyglutaric aciduria. Proc Natl Acad Sci U S A, 101:16849–16854. 2004.
265.
RzemR, VincentMF, Van SchaftingenE, Veiga-da-CunhaM. L-2-hydroxyglutaric aciduria, a defect of metabolite repair. J Inherit Metab Dis, 30:681–689. 2007.
266.
SalahudeenAA, BruickRK. Maintaining Mammalian iron and oxygen homeostasis: sensors, regulation, and cross-talk. Ann N Y Acad Sci, 1177:30–38. 2009.
267.
SalminenA, KaarnirantaK. SIRT1 regulates the ribosomal DNA locus: epigenetic candles twinkle longevity in the Christmas tree. Biochem Biophys Res Commun, 378:6–9. 2009.
268.
SalnikowK, AnWG, MelilloG, BlagosklonnyMV, CostaM. Nickel-induced transformation shifts the balance between HIF-1 and p53 transcription factors. Carcinogenesis, 20:1819–1823. 1999.
269.
SalnikowK, BlagosklonnyMV, RyanH, JohnsonR, CostaM. Carcinogenic nickel induces genes involved with hypoxic stress. Cancer Res, 60:38–41. 2000.
270.
SandmeierJJ, CelicI, BoekeJD, SmithJS. Telomeric and rDNA silencing in Saccharomyces cerevisiae are dependent on a nuclear NAD(+) salvage pathway. Genetics, 160:877–889. 2002.
271.
Santos-RosaH, SchneiderR, BannisterAJ, SherriffJ, BernsteinBE, EmreNC, SchreiberSL, MellorJ, KouzaridesT. Active genes are tri-methylated at K4 of histone H3. Nature, 419:407–411. 2002.
272.
Santos-RosaH, SchneiderR, BernsteinBE, KarabetsouN, MorillonA, WeiseC, SchreiberSL, MellorJ, KouzaridesT. Methylation of histone H3 K4 mediates association of the Isw1p ATPase with chromatin. Mol Cell, 12:1325–1332. 2003.
273.
SawantRR, VazeO, RockwellK, TorchilinVP. Palmitoyl ascorbate-modified liposomes as nanoparticle platform for ascorbate-mediated cytotoxicity and paclitaxel co-delivery. Eur J Pharm Biopharm, 75:321–326. 2010.
274.
SaxonovS, BergP, BrutlagDL. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci U S A, 103:1412–1417. 2006.
275.
SchaeferM, LykoF. Solving the Dnmt2 enigma. Chromosoma, 119:35–40. 2010.
SelakMA, ArmourSM, MacKenzieED, BoulahbelH, WatsonDG, MansfieldKD, PanY, SimonMC, ThompsonCB, GottliebE. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell, 7:77–85. 2005.
278.
SelakMA, DuranRV, GottliebE. Redox stress is not essential for the pseudo-hypoxic phenotype of succinate dehydrogenase deficient cells. Biochim Biophys Acta, 1757:567–572. 2006.
279.
SharmaP, KumarJ, GargG, KumarA, PatowaryA, KarthikeyanG, RamakrishnanL, BrahmachariV, SenguptaS. Detection of altered global DNA methylation in coronary artery disease patients. DNA Cell Biol, 27:357–365. 2008.
280.
ShiY, LanF, MatsonC, MulliganP, WhetstineJR, ColePA, CaseroRA. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell, 119:941–953. 2004.
281.
ShoreD, SquireM, NasmythKA. Characterization of two genes required for the position-effect control of yeast mating-type genes. EMBO J, 3:2817–2823. 1984.
282.
SiedleckiP, ZielenkiewiczP. Mammalian DNA methyltransferases. Acta Biochim Pol, 53:245–256. 2006.
283.
SmithBC, DenuJM. Chemical mechanisms of histone lysine and arginine modifications. Biochim Biophys Acta, 1789:45–57. 2009.
284.
SmithBC, HallowsWC, DenuJM. Mechanisms and molecular probes of sirtuins. Chem Biol, 15:1002–1013. 2008.
285.
SmithEH, JanknechtR, MaherLJ3rd. Succinate inhibition of alpha-ketoglutarate-dependent enzymes in a yeast model of paraganglioma. Hum Mol Genet, 16:3136–3148. 2007.
286.
SmithJS, BrachmannCB, CelicI, KennaMA, MuhammadS, StaraiVJ, AvalosJL, Escalante-SemerenaJC, GrubmeyerC, WolbergerCet al.A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family. Proc Natl Acad Sci U S A, 97:6658–6663. 2000.
287.
SomozaJR, SkeneRJ, KatzBA, MolC, HoJD, JenningsAJ, LuongC, ArvaiA, BuggyJJ, ChiEet al.Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. Structure, 12:1325–1334. 2004.
288.
SpannhoffA, HauserAT, HeinkeR, SipplW, JungM. The emerging therapeutic potential of histone methyltransferase and demethylase inhibitors. ChemMedChem, 4:1568–1582. 2009.
289.
StrahlBD, OhbaR, CookRG, AllisCD. Methylation of histone H3 at lysine 4 is highly conserved and correlates with transcriptionally active nuclei in Tetrahymena. Proc Natl Acad Sci U S A, 96:14967–14972. 1999.
290.
StruysEA. D-2-Hydroxyglutaric aciduria: unravelling the biochemical pathway and the genetic defect. J Inherit Metab Dis, 29:21–29. 2006.
291.
StruysEA, VerhoevenNM, JansenEE, Ten BrinkHJ, GuptaM, BurlingameTG, QuangLS, MaherT, RinaldoP, SneadOCet al.Metabolism of gamma-hydroxybutyrate to d-2-hydroxyglutarate in mammals: further evidence for d-2-hydroxyglutarate transhydrogenase. Metabolism, 55:353–358. 2006.
292.
SuWY, XiongH, FangJY. Natural antisense transcripts regulate gene expression in an epigenetic manner. Biochem Biophys Res Commun, 396:177–181. 2010.
293.
SunH, ZhouX, ChenH, LiQ, CostaM. Modulation of histone methylation and MLH1 gene silencing by hexavalent chromium. Toxicol Appl Pharmacol, 237:258–266. 2009.
294.
SundenSL, RenduchintalaMS, ParkEI, MiklaszSD, GarrowTA. Betaine-homocysteine methyltransferase expression in porcine and human tissues and chromosomal localization of the human gene. Arch Biochem Biophys, 345:171–174. 1997.
295.
SuzukiMM, BirdA. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet, 9:465–76. 2008.
296.
Szent-GyörgyiA. Electronic Biology and Cancer: A New Theory of Cancer. New York, NY: Marcel Dekker, 1976.
297.
TahilianiM, KohKP, ShenY, PastorWA, BandukwalaH, BrudnoY, AgarwalS, IyerLM, LiuDR, AravindLet al.Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by the MLL Fusion Partner TET1. Science, 324:930–935. 2009.
298.
TakeuchiT, YamazakiY, Katoh-FukuiY, TsuchiyaR, KondoS, MotoyamaJ, HigashinakagawaT. Gene trap capture of a novel mouse gene, jumonji, required for neural tube formation. Genes Dev, 9:1211–1222. 1995.
299.
TalTL, SimmonsSO, SilbajorisR, DaileyL, ChoSH, RamabhadranR, LinakW, ReedW, BrombergPA, SametJM. Differential transcriptional regulation of IL-8 expression by human airway epithelial cells exposed to diesel exhaust particles. Toxicol Appl Pharmacol, 243:46–54. 2010.
300.
TannerKG, LandryJ, SternglanzR, DenuJM. Silent information regulator 2 family of NAD- dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose. Proc Natl Acad Sci U S A, 97:14178–14182. 2000.
301.
TannyJC, DowdGJ, HuangJ, HilzH, MoazedD. An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing. Cell, 99:735–745. 1999.
302.
TheilEC, GossDJ. Living with iron (and oxygen): questions and answers about iron homeostasis. Chem Rev, 109:4568–4579. 2009.
303.
ThompsonPR, FastW. Histone citrullination by protein arginine deiminase: is arginine methylation a green light or a roadblock?ACS Chem Biol, 1:433–441. 2006.
304.
TomasettiM, StrafellaE, StaffolaniS, SantarelliL, NeuzilJ, GuerrieriR. alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate. Br J Cancer, 102:1224–1234. 2010.
305.
TretterL, Adam-ViziV. Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress. Philos Trans R Soc Lond B Biol Sci, 360:2335–2345. 2005.
306.
TrewickSC, HenshawTF, HausingerRP, LindahlT, SedgwickB. Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage. Nature, 419:174–178. 2002.
307.
TrewickSC, McLaughlinPJ, AllshireRC. Methylation: lost in hydroxylation?EMBO Rep, 6:315–320. 2005.
308.
TsukadaY, FangJ, Erdjument-BromageH, WarrenME, BorchersCH, TempstP, ZhangY. Histone demethylation by a family of JmjC domain-containing proteins. Nature, 439:811–816. 2006.
309.
TulinA, ChinenovY, SpradlingA. Regulation of chromatin structure and gene activity by poly(ADP-ribose) polymerases. Curr Top Dev Biol, 56:55–83. 2003.
UedaK, OmachiA, KawaichiM, HayaishiO. Natural occurrence of poly(ADP-ribosyl) histones in rat liver. Proc Natl Acad Sci U S A, 72:205–209. 1975.
314.
UedaR, SuzukiT, MinoK, TsumotoH, NakagawaH, HasegawaM, SasakiR, MizukamiT, MiyataN. Identification of cell-active lysine specific demethylase 1-selective inhibitors. J Am Chem Soc, 131:17536–17537. 2009.
315.
Van SchaftingenE, RzemR, Veiga-da-CunhaM. L: −2-hydroxyglutaric aciduria, a disorder of metabolite repair. J Inherit Metab Dis, 32:135–142. 2009.
316.
Vander HeidenMG, CantleyLC, ThompsonCB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science, 324:1029–1033. 2009.
317.
VaramballyS, CaoQ, ManiRS, ShankarS, WangX, AteeqB, LaxmanB, CaoX, JingX, RamnarayananKet al.Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science, 322:1695–1699. 2008.
318.
VillagraA, ChengF, WangHW, SuarezI, GlozakM, MaurinM, NguyenD, WrightKL, AtadjaPW, BhallaKet al.The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance. Nat Immunol, 10:92–100. 2009.
319.
VissersMC, WilkieRP. Ascorbate deficiency results in impaired neutrophil apoptosis and clearance and is associated with up-regulation of hypoxia-inducible factor 1alpha. J Leukoc Biol, 81:1236–1244. 2007.
320.
WaddingtonCH. The epigenetics of birds. Cambridge,UK: Cambridge University Press, 1952.
WamelinkMM, StruysEA, JakobsC. The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review. J Inherit Metab Dis, 31:703–717. 2008.
WarburgO. On the origin of cancer cells. Science, 123:309–314. 1956.
325.
WarburgO, PosenerK, NegeleinE. On the metabolism of carcinoma cells. Biochemische Zeitschrift, 152:309–344. 1924.
326.
This reference has been deleted.
327.
WenYD, PerissiV, StaszewskiLM, YangWM, KronesA, GlassCK, RosenfeldMG, SetoE. The histone deacetylase-3 complex contains nuclear receptor corepressors. Proc Natl Acad Sci U S A, 97:7202–7207. 2000.
328.
WiesenJL, TomasiTB. Dicer is regulated by cellular stresses and interferons. Mol Immunol, 46:1222–1228. 2009.
329.
WittO, DeubzerHE, MildeT, OehmeI. HDAC family: what are the cancer relevant targets?Cancer Lett, 277:8–21. 2009.
330.
WnekSM, JensenTJ, SeversonPL, FutscherBW, GandolfiAJ. Monomethylarsonous acid produces irreversible events resulting in malignant transformation of a human bladder cell line following 12 weeks of low-level exposure. Toxicol Sci, 116:44–57. 2010.
331.
WysockaJ, AllisCD, CoonrodS. Histone arginine methylation and its dynamic regulation. Front Biosci, 11:344–355. 2006.
332.
YamakuchiM, FerlitoM, LowensteinCJ. miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci U S A, 105:13421–13426. 2008.
333.
YanY, KluzT, ZhangP, ChenHB, CostaM. Analysis of specific lysine histone H3 and H4 acetylation and methylation status in clones of cells with a gene silenced by nickel exposure. Toxicol Appl Pharmacol, 190:272–277. 2003.
334.
YangSR, ChidaAS, BauterMR, ShafiqN, SeweryniakK, MaggirwarSB, KiltyI, RahmanI. Cigarette smoke induces proinflammatory cytokine release by activation of NF-kappaB and posttranslational modifications of histone deacetylase in macrophages. Am J Physiol Lung Cell Mol Physiol, 291:L46–L57. 2006.
335.
YeH, RouaultTA. Human iron-sulfur cluster assembly, cellular iron homeostasis, and disease. Biochemistry, 49:4945–4956. 2010.
336.
YidengJ, JianzhongZ, YingH, JuanS, JingeZ, ShenglanW, XiaoqunH, ShurenW. Homocysteine-mediated expression of SAHH, DNMTs, MBD2, and DNA hypomethylation potential pathogenic mechanism in VSMCs. DNA Cell Biol, 26:603–611. 2007.
337.
YidengJ, ZhihongL, JiantuanX, JunC, GuizhongL, ShurenW. Homocysteine-mediated PPARalpha,gamma DNA methylation and its potential pathogenic mechanism in monocytes. DNA Cell Biol, 27:143–150. 2008.
338.
YuanJ, PuM, ZhangZ, LouZ. Histone H3-K56 acetylation is important for genomic stability in mammals. Cell Cycle, 8:1747–1753. 2009.
339.
ZakhariS. Overview: how is alcohol metabolized by the body?Alcohol Res Health, 29:245–254. 2006.
340.
ZardoG, CaiafaP. The unmethylated state of CpG islands in mouse fibroblasts depends on the poly(ADP-ribosyl)ation process. J Biol Chem, 273:16517–16520. 1998.
341.
ZardoG, MarenziS, PerilliM, CaiafaP. Inhibition of poly(ADP-ribosyl)ation introduces an anomalous methylation pattern in transfected foreign DNA. FASEB J, 13:1518–1522. 1999.
342.
ZardoG, RealeA, De MatteisG, BuontempoS, CaiafaP. A role for poly(ADP-ribosyl)ation in DNA methylation. Biochem Cell Biol, 81:197–208. 2003.
343.
ZardoG, RealeA, PassanantiC, PradhanS, BuontempoS, DeMatteis G, AdamsRL, CaiafaP. Inhibition of poly(ADP-ribosyl)ation induces DNA hypermethylation: a possible molecular mechanism. FASEB J, 16:1319–1321. 2002.
ZhangAS, EnnsCA. Molecular mechanisms of normal iron homeostasis. Hematol Am Soc Hematol Educ Program, 207–214. 2009.
346.
ZhangJ. Are poly(ADP-ribosyl)ation by PARP-1 and deacetylation by Sir2 linked?Bioessays, 25:808–814. 2003.
347.
ZhangQ, PistonDW, GoodmanRH. Regulation of corepressor function by nuclear NADH. Science, 295:1895–1897. 2002.
348.
ZhangT, BerrocalJG, FrizzellKM, GambleMJ, DuMondME, KrishnakumarR, YangT, SauveAA, KrausWL. Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene promoters. J Biol Chem, 284:20408–20417. 2009.
349.
ZhangY, MarcillatO, GiuliviC, ErnsterL, DaviesKJ. The oxidative inactivation of mitochondrial electron transport chain components and ATPase. J Biol Chem, 265:16330–16336. 1990.
350.
ZhangZ, RenJ, HarlosK, McKinnonCH, CliftonIJ, SchofieldCJ. Crystal structure of a clavaminate synthase-Fe(II)-2-oxoglutarate-substrate-NO complex: evidence for metal centered rearrangements. FEBS Lett, 517:7–12. 2002.
