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An Overview of Epigenetic Mechanisms in Health and Disease

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Molecular mechanisms and physiology of disease

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Abstract

Epigenetic modifications are emerging as key players in not only the regulation of normal genomic expression patterns, but also their role in disease progression due to their deregulation. An irregular change in DNA methylation, either through aberrant hypermethylation or hypomethylation, may have serious consequences relating to carcinogenesis by potentiating or preventing gene functions. Conversely, the reversal of abnormal hypermethylation has been aided by the advent of DNMT inhibitors to restore tumour suppressor gene function. In addition, the field of histone post-translational modifications (PTMs) is expanding. The best characterised and seemingly most involved in pathogenesis remain acetylation and methylation of amino acid residues within N-terminal tails. As the complexity of the epigenetic language becomes more apparent, it has been found that there is significant crosstalk between modifications, including DNA methylation and histone PTMs. Great promise lies in the development of histone deacetylase inhibiting compounds, which initiate a vast number of effects normalising or eradicating tumour cells.

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References

  • Alcazar O, Achberger S, Aldrich W, Hu ZB, Negrotto S, Saunthararajah Y, Triozzi P (2012) Epigenetic regulation by decitabine of melanoma differentiation in vitro and in vivo. Int J Cancer 131:18–29

    CAS  PubMed Central  PubMed  Google Scholar 

  • Allfrey VG, Faulkner R, Mirsky AE (1964) Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc Natl Acad Sci U S A 51:786–794

    CAS  PubMed Central  PubMed  Google Scholar 

  • Al-Salihi M, Yu M, Burnett DM, Alexander A, Samlowski W, Fitzpatrick FA (2011) The depletion of DNA methyltransferase-1 and the epigenetic effects of 5-aza-2′ deoxycytidine (decitabine) are differentially regulated by cell cycle progression. Epigenetics 6:1021–1028

    CAS  PubMed Central  PubMed  Google Scholar 

  • Antequera F (2003) Structure, function and evolution of CpG island promoters. Cell Mol Life Sci 60:1647–1658

    CAS  PubMed  Google Scholar 

  • Atadja PW (2011) HDAC inhibitors and cancer therapy. Prog Drug Res 67:175–95

    CAS  PubMed  Google Scholar 

  • Bali P, Pranpat M, Bradner J, Balasis M, Fiskus W, Guo F, Rocha K, Kumaraswamy S, Boyapalle S, Atadja P, Seto E, Bhalla K (2005) Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors. J Biol Chem 280:26729–26734

    CAS  PubMed  Google Scholar 

  • Ballas N, Battaglioli E, Atouf F, Andres ME, Chenoweth J, Anderson ME, Burger C, Moniwa M, Davie JR, Bowers WJ, Federoff HJ, Rose DW, Rosenfeld MG, Brehm P, Mandel G (2001) Regulation of neuronal traits by a novel transcriptional complex. Neuron 31:353–365

    CAS  PubMed  Google Scholar 

  • Bedford MT (2007) Arginine methylation at a glance. J Cell Sci 120:4243–4246

    CAS  PubMed  Google Scholar 

  • Bedford MT, Clarke SG (2009) Protein arginine methylation in mammals: who, what, and why. Mol Cell 33:1–13

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bednar J, Horowitz RA, Grigoryev SA, Carruthers LM, Hansen JC, Koster AJ, Woodcock CL (1998) Nucleosomes, linker DNA, and linker histone form a unique structural motif that directs the higher-order folding and compaction of chromatin. Proc Natl Acad Sci U S A 14173

    Google Scholar 

  • Bertino EM, Otterson GA (2011) Romidepsin: a novel histone deacetylase inhibitor for cancer. Expert Opin Investig Drugs 20:1151–1158

    CAS  PubMed  Google Scholar 

  • Bestor TH, Gundersen G, Kolsto AB, Prydz H (1992) Cpg islands in mammalian gene promoters are inherently resistant to de novo methylation. Genet Anal Tech Appl 9(2):48–53 [Accessed 12 Dec 2012]

    CAS  PubMed  Google Scholar 

  • Bing X, Jonathan RW, Steven JG (2003) SET domains and histone methylation. Curr Opin Struct Biol 13:699–705

    Google Scholar 

  • Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21

    CAS  PubMed  Google Scholar 

  • Bird AP, Wolffe AP (1999) Methylation-induced repression—belts, braces, and chromatin. Cell 99:451–454

    CAS  PubMed  Google Scholar 

  • Bishop TC (2008) Geometry of the nucleosomal DNA superhelix. Biophys J 95:1007–1017

    CAS  PubMed Central  PubMed  Google Scholar 

  • Black JC, Van Rechem C, Whetstine JR (2012) Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol Cell 48:491–507

    CAS  PubMed  Google Scholar 

  • Bottomley MJ, Lo Surdo P, Di Giovine P, Cirillo A, Scarpelli R, Ferrigno F, Jones P, Neddermann P, De Francesco R, Steinkuhler C, Gallinari P, Carfi A (2008) Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain. J Biol Chem 283:26694–26704

    CAS  PubMed Central  PubMed  Google Scholar 

  • Boyault C, Zhang Y, Fritah S, Caron C, Gilquin B, Kwon SH, Garrido C, Yao TP, Vourc’h C, Matthias P, Khochbin S (2007) HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates. Genes Dev 21:2172–2181

    CAS  PubMed Central  PubMed  Google Scholar 

  • Brady ME, Ozanne DM, Gaughan L, Waite I, Cook S, Neal DE, Robson CN (1999) Tip60 is a nuclear hormone receptor coactivator. J Biol Chem 274:17599–17604

    CAS  PubMed  Google Scholar 

  • Brent B-T, David AW, Robert MF, John TL, Kraus WL, Michelle DW (2004) Specific contributions of histone tails and their acetylation to the mechanical stability of nucleosomes. J Mol Biol 346:135–146

    Google Scholar 

  • Campbell JJ, Clark RA, Watanabe R, Kupper TS (2010) Sezary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors. Blood 116:767–771

    CAS  PubMed Central  PubMed  Google Scholar 

  • Carew JS, Medina EC, Esquivel JA II, Mahalingam D, Swords R, Kelly K, Zhang H, Huang P, Mita AC, Mita MM, Giles FJ, Nawrocki ST (2010) Autophagy inhibition enhances vorinostat-induced apoptosis via ubiquitinated protein accumulation. J Cell Mol Med 14:2448–2459

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cea M, Soncini D, Fruscione F, Raffaghello L, Garuti A, Emionite L, Moran E, Magnone M, Zoppoli G, Reverberi D, Caffa I, Salis A, Cagnetta A, Bergamaschi M, Casciaro S, Pierri I, Damonte G, Ansaldi F, Gobbi M, Pistoia V, Ballestrero A, Patrone F, Bruzzone S, Nencioni A (2011) Synergistic interactions between HDAC and sirtuin inhibitors in human leukemia cells. PLoS One 6:12p

    Google Scholar 

  • Chang S, Young BD, Li S, Qi X, Richardson JA, Olson EN (2006) Histone deacetylase 7 maintains vascular integrity by repressing matrix metalloproteinase 10. Cell 126:321–334

    CAS  PubMed  Google Scholar 

  • Chen L, Dahlstrom JE, Lee SH, Rangasamy D (2012) Naturally occurring endo-siRNA silences LINE-1 retrotransposons in human cells through DNA methylation. Epigenetics 7:758–771

    CAS  PubMed  Google Scholar 

  • Choi J (2010) Constrasting chromatin organization of CpG islands and exons in the human genome. Genome Biol 11(7):R70

    PubMed Central  PubMed  Google Scholar 

  • Choi JY, James SR, Link PA, McCann SE, Hong CC, Davis W, Nesline MK, Ambrosone CB, Karpf AR (2009) Association between global DNA hypomethylation in leukocytes and risk of breast cancer. Carcinogenesis 30:1889–1897

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cimato TR, Tang J, Xu Y, Guarnaccia C, Herschman HR, Pongor S, Aletta JM (2002) Nerve growth factor-mediated increases in protein methylation occur predominantly at type I arginine methylation sites and involve protein arginine methyltransferase 1. J Neurosci Res 67:435–442

    CAS  PubMed  Google Scholar 

  • Cloos PAC, Christensen J, Agger K, Helin K (2008) Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease. Genes Dev 22:1115–1140

    CAS  PubMed Central  PubMed  Google Scholar 

  • Coiffier B, Pro B, Prince HM, Foss F, Sokol L, Greenwood M, Caballero D, Borchmann P, Morschhauser F, Wilhelm M, Pinter-Brown L, Padmanabhan S, Shustov A, Nichols J, Carroll S, Balser J, Balser B, Horwitz S (2012) Results from a pivotal, open-label, Phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol 30:631–636

    CAS  PubMed  Google Scholar 

  • Collins RE, Tachibana M, Tamaru H, Smith KM, Jia D, Zhang X, Selker EU, Shinkai Y, Cheng X (2005) In vitro and in vivo analyses of a Phe/Tyr switch controlling product specificity of histone lysine methyltransferases. J Biol Chem 280:5563–5570

    CAS  PubMed Central  PubMed  Google Scholar 

  • Corn PG, Heath EI, Heitmiller R, Fogt F, Forastiere AA, Herman JG, Wu T-T (2001) Frequent hypermethylation of the 5′ CpG island of E-cadherin in esophageal adenocarcinoma. Clin Cancer Res 7:2765–2769

    CAS  PubMed  Google Scholar 

  • Cote J, Richard S (2005) Tudor domains bind symmetrical dimethylated arginines. J Biol Chem 280:28476–28483

    CAS  PubMed  Google Scholar 

  • Damaraju VL, Mowles D, Yao S, Ng A, Young JD, Cass CE, Tong Z (2012) Role of human nucleoside transporters in the uptake and cytotoxicity of azacitidine and decitabine. Nucleosides Nucleotides Nucleic Acids 31:236–255

    CAS  PubMed  Google Scholar 

  • Davuluri RV, Grosse I, Zhang MQ (2001) Computational identification of promoters and first exons in the human genome. Nat Genet 29(4):412–7

    CAS  PubMed  Google Scholar 

  • De Smet C, Lurquin C, Lethe B, Martelange V, Boon T (1999) DNA methylation is the primary silencing mechanism for a set of germ line- and tumor-specific genes with a CpG-rich promoter. Mol Cell Biol 19:7327–7335

    PubMed Central  PubMed  Google Scholar 

  • Decarlo D, Hadden MK (2012) Oncoepigenomics: making histone lysine methylation count. Eur J Med Chem 56:179–194

    CAS  PubMed  Google Scholar 

  • Delgado-Cruzata L, Wu HC, Perrin M, Liao YY, Kappil MA, Ferris JS, Flom JD, Yazici H, Santella RM, Terry MB (2012) Global DNA methylation levels in white blood cell DNA from sisters discordant for breast cancer from the New York site of the breast cancer family registry. Epigenetics 7:868–874

    CAS  PubMed Central  PubMed  Google Scholar 

  • Di Lorenzo A, Bedford MT (2011) Histone arginine methylation. FEBS Lett 585:2024–2031

    PubMed Central  PubMed  Google Scholar 

  • Du JT, Zhou YY, Su XY, Yu JJ, Khan S, Jiang H, Kim J, Woo J, Kim JH, Choi BH, He B, Chen W, Zhang S, Cerione RA, Auwerx J, Hao Q, Lin HN (2011) Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science 334:806–809

    CAS  PubMed Central  PubMed  Google Scholar 

  • Duvic M, Talpur R, Ni X, Zhang C, Hazarika P, Kelly C, Chiao JH, Reilly JF, Ricker JL, Richon VM, Frankel SR (2007) Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood 109:31–39

    CAS  PubMed Central  PubMed  Google Scholar 

  • Eckhardt F, Lewin J, Cortese R, Rakyan VK, Attwood J, Burger M, Burton J, Cox TV, Davies R, Down TA, Haefliger C, Horton R, Howe K, Jackson DK, Kunde J, Koenig C, Liddle J, Niblett D, Otto T, Pettett R (2006) DNA methylation profiling of human chromosomes 6, 20 and 22. Nat Genet 38:1378–1385

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ehrlich M (2002) DNA methylation in cancer: too much, but also too little. Oncogene 21:5400

    CAS  PubMed  Google Scholar 

  • Eisenberg-Lerner A, Kimchi A (2009) The paradox of autophagy and its implication in cancer etiology and therapy. Apoptosis 14:376–391

    PubMed  Google Scholar 

  • El-Khoury V, Breuzard G, Fourré N, Dufer J (2007) The histone deacetylase inhibitor trichostatin A downregulates human MDR1 (ABCB1) gene expression by a transcription-dependent mechanism in a drug-resistant small cell lung carcinoma cell line model. Br J Cancer 97:562–573

    CAS  PubMed Central  PubMed  Google Scholar 

  • Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB, HERMAN JG (1999) Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. Cancer Res 59:67–70

    CAS  PubMed  Google Scholar 

  • Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG (2000a) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343:1350–1354

    CAS  PubMed  Google Scholar 

  • Esteller M, Sparks A, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA, Gonzalez S, Tarafa G, Sidransky D, Meltzer SJ, Baylin SB, Herman JG (2000b) Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. Cancer Res 60:4366–4371

    CAS  PubMed  Google Scholar 

  • Esteller M, Corn PG, Baylin SB, Herman JG (2001) A gene hypermethylation profile of human cancer. Cancer Res 72

    Google Scholar 

  • Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301:89–92

    CAS  PubMed  Google Scholar 

  • Feinberg AP, Ohlsson R, Henikoff S (2006) The epigenetic progenitor origin of human cancer. Nat Rev Genet 7:21–33

    CAS  PubMed  Google Scholar 

  • Finch JT, Klug A (1976) Solenoidal model for superstructure in chromatin. Proc Natl Acad Sci U S A 1897

    Google Scholar 

  • Firestein R, Blander G, Michan S, Oberdoerffer P, Ogino S, Campbell J, Bhimavarapu A, Luikenhuis S, DE Cabo R, Fuchs C, Hahn WC, Guarente LP, Sinclair DA (2008) The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS One 3:1–9

    Google Scholar 

  • Fischle W, Kiermer V, Dequiedt F, Verdin E (2001) The emerging role of class II histone deacetylases. Biochem Cell Biol 79:337–348

    CAS  PubMed  Google Scholar 

  • Fischle W, Dequiedt F, Hendzel MJ, Guenther MG, Lazar MA, Voelter W, Verdin E (2002) Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR. Mol Cell 9:45–57

    CAS  PubMed  Google Scholar 

  • Francesca B, Elena S, Erico M, Antonella G, Alessandro S, Alberto B, Germano F, Valeria S (2011) Proteomic analysis identifies differentially expressed proteins in AML1/ETO acute myeloid leukemia cells treated with DNMT inhibitors azacitidine and decitabine. Leuk Res 36:607–618

    Google Scholar 

  • Gao L, Cueto MA, Asselbergs F, Atadja P (2002) Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J Biol Chem 277:25748–25755

    CAS  PubMed  Google Scholar 

  • Gardner KE, Allis CD, Strahl BD (2011) Operating on chromatin, a colorful language where context matters. J Mol Biol 409:36–46

    CAS  PubMed Central  PubMed  Google Scholar 

  • Geng H, Harvey CT, Pittsenbarger J, Liu Q, Beer TM, Xue C, Qian DZ (2011) HDAC4 protein regulates HIF1α protein lysine acetylation and cancer cell response to hypoxia. J Biol Chem 286:38095–38102

    CAS  PubMed Central  PubMed  Google Scholar 

  • Giralt A, Villarroya F (2012) SIRT3, a pivotal actor in mitochondrial functions: metabolism, cell death and aging. Biochem J 444:1–10

    CAS  PubMed  Google Scholar 

  • Glover AB, Leyland-Jones B (1987) Biochemistry of azacitidine: a review. Cancer Treat Rep 71:959–964

    CAS  PubMed  Google Scholar 

  • Goll MG, Bestor TH (2005) Eukaryotic cytosine methyltransferases. Annu Rev Biochem 74:481–514

    CAS  PubMed  Google Scholar 

  • Gonzalez-Zulueta M, Bender CM, Yang AS, Nguyen T, Beart RW, Van Tornout JM, Jones PA (1995) Methylation of the 5′ CpG island of the p16/CDKN2 tumor suppressor gene in normal and transformed human tissues correlates with gene silencing. Cancer Res 55:4531–4535

    CAS  PubMed  Google Scholar 

  • Grigoryev SA, Arya G, Correll S, Woodcock CL, Schlick T (2011) Evidence for heteromorphic chromatin fibers from analysis of nucleosome interactions. Proc Natl Acad Sci U S A 106:13317–13322

    Google Scholar 

  • Grozinger CM, Schreiber SL (2002) Deacetylase enzymes: biological functions and the use of small-molecule inhibitors. Chem Biol 9:3–16

    CAS  PubMed  Google Scholar 

  • Guenther MG, Barak O, Lazar MA (2001) The SMRT and N-CoR corepressors are activating cofactors for histone deacetylase 3. Mol Cell Biol 21:6091–6101

    CAS  PubMed Central  PubMed  Google Scholar 

  • Guo H-B, Guo H (2007) Mechanism of histone methylation catalyzed by protein lysine methyltransferase SET7/9 and origin of product specificity. Proc Natl Acad Sci U S A 104:8797–8802

    CAS  PubMed Central  PubMed  Google Scholar 

  • Haberland M, Montgomery RL, Olson EN (2009) The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 10:32–42

    CAS  PubMed Central  PubMed  Google Scholar 

  • Herman JG, Merlo A, Mao L, Lapidus RG, Issa JP, Davidson NE, Sidransky D, Baylin SB (1995) Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res 55:4525–4530

    CAS  PubMed  Google Scholar 

  • Hermann A, Gowher H, Jeltsch A (2004a) Biochemistry and biology of mammalian DNA methyltransferases. Cell Mol Life Sci 61:2571–2587

    CAS  PubMed  Google Scholar 

  • Hermann A, Goyal R, Jeltsch A (2004b) The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites. J Biol Chem 279:48350–48359

    CAS  PubMed  Google Scholar 

  • Herrera JE, Bergel M, Yang X-J, Nakatani Y, Bustin M (1997) The histone acetyltransferase activity of human GCN5 and PCAF is stabilized by coenzymes. J Biol Chem 272:27253–27258

    CAS  PubMed  Google Scholar 

  • Hollenbach PW, Nguyen AN, Brady H, Williams M, Ning Y, Richard N, Krushel L, Aukerman SL, Heise C, Macbeth KJ (2004) A comparison of azacitidine and decitabine activities in acute myeloid leukemia cell lines. PLoS One 5:1–10

    Google Scholar 

  • Hong L, Schroth GP, Matthews HR, Yau P, Bradbury EM (1993) Studies of the DNA binding properties of histone H4 amino terminus. Thermal denaturation studies reveal that acetylation markedly reduces the binding constant of the H4 “tail” to DNA. J Biol Chem 268:305–314

    CAS  PubMed  Google Scholar 

  • Huang N, Mackerell AD Jr (2004) Atomistic view of base flipping in DNA. Philos Trans A Math Phys Eng Sci 362:1439–1460

    CAS  PubMed  Google Scholar 

  • Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, Yoshida M, Wang X-F, Yao T-P (2002) HDAC6 is a microtubule-associated deacetylase. Nature 417:455–458

    CAS  PubMed  Google Scholar 

  • Insinga A, Monestiroli S, Ronzoni S, Gelmetti V, Marchesi F, Viale A, Altucci L, Nervi C, Minucci S, Pelicci PG (2005) Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway. Nat Med 11:71–76

    CAS  PubMed  Google Scholar 

  • Jiang JF, Lu JY, Lu D, Liang ZJ, Li LC, Ouyang SS, Kong XQ, Jiang HL, Shen BR, Luo C (2012) Investigation of the acetylation mechanism by GCN5 histone acetyltransferase. PLoS One 7:13p

    Google Scholar 

  • Jin Z, Dicker DT, El-Deiry WS (2002) Enhanced sensitivity of G1 arrested human cancer cells suggests a novel therapeutic strategy using a combination of simvastatin and TRAIL. Cell Cycle 1:82–89

    CAS  PubMed  Google Scholar 

  • Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, Strouboulis J, Wolffe AP (1998) Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 19:187–191

    CAS  PubMed  Google Scholar 

  • Kantarjian H, Issa JPJ, Rosenfeld CS, Bennett JM, Albitar M, Dipersio J, Klimek V, Slack J, De Castro C, Ravandi F, Helmer R, Shen LL, Nimer SD, Leavitt R, Raza A, Saba H (2006) Decitabine improves patient outcomes in myelodysplastic syndromes—resuits of a phase III randomized study. Cancer 106:1794–1803

    CAS  PubMed  Google Scholar 

  • Keating GM (2011) Azacitidine: a review of its use in the management of myelodysplastic syndromes/acute myeloid leukaemia. Drugs 72:1111–1136

    Google Scholar 

  • Keith BG, Junling L, Michael JS, Ru-Qi W, Daniel HA, Steven KD (2003) Role of Class I and Class II histone deacetylases in carcinoma cells using siRNA. Biochem Biophys Res Commun 310:529–536

    Google Scholar 

  • Kim W, Kim R, Park G, Park J-W, Kim J-E (2011) Deficiency of H3K79 histone methyltransferase Dot1-like protein (DOT1L) inhibits cell proliferation. J Biol Chem 287:5588–5599

    PubMed Central  PubMed  Google Scholar 

  • Kleinschmidt MA, Streubel G, Samans B, Krause M, Bauer U-M (2008) The protein arginine methyltransferases CARM1 and PRMT1 cooperate in gene regulation. Nucleic Acids Res 36:3202–3213

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kong XG, Lin Z, Liang DM, Fath D, Sang NL, Caro J (2006) Histone deacetylase inhibitors induce VHL and ubiquitin-independent proteasomal degradation of hypoxia-inducible factor 1 alpha. Mol Cell Biol 26:2019–2028

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705

    CAS  PubMed  Google Scholar 

  • Kramer OH, Muller S, Reichardt S, Heinzel T (2008) Mechanism for ubiquitylation of the leukemia fusion proteins AML1-ETO and PML-RAR alpha. FASEB J 22

    Google Scholar 

  • Lacoste N, Coté J (2003) Le code épigénétique des histones. Med Sci 19:955–959

    Google Scholar 

  • Lahm A, Paolini C, Pallaoro M, Nardi MC, Jones P, Neddermann P, Sambucini S, Bottomley MJ, Lo Surdo P, Carfí A, Koch U, De Francesco R, Steinkühler C, Gallinari P (2007) Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases. Proc Natl Acad Sci U S A 104:17335–17340

    CAS  PubMed Central  PubMed  Google Scholar 

  • Laird PW (2003) The power and the promise of DNA methylation markers. Nat Rev Cancer 3:253–266

    CAS  PubMed  Google Scholar 

  • Le Guezennec X, Vermeulen M, Brinkman A, Hoeijmakers W, Cohen A, Lasonder E, Stunnenberg H (2006) MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical and functional properties. Mol Cell Biol 26:843–851

    PubMed Central  PubMed  Google Scholar 

  • Lee S, Lee HJ, Kim JH, Lee HS, Jang JJ, Kang GH (2003) Aberrant CpG island hypermethylation along multistep hepatocarcinogenesis. Am J Pathol 163:1371–1378

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee Y-S, Lim K-H, Guo X, Kawaguchi Y, Gao Y, Barrientos T, Ordentlich P, Wang X-F, Counter CM, Yao T-P (2008) The cytoplasmic deacetylase HDAC6 is required for efficient oncogenic tumorigenesis. Cancer Res 68:7561–7569

    CAS  PubMed Central  PubMed  Google Scholar 

  • Leone G, Teofili L, Voso MT, Lubbert M (2002) DNA methylation and demethylating drugs in myelodysplastic syndromes and secondary leukemias. Haematologica 87:1324–1341

    CAS  PubMed  Google Scholar 

  • Li C-T, Hsiao Y-M, Wu T-C, Lin Y-W, Yeh K-T, Ko J-L (2011a) Vorinostat, SAHA, represses telomerase activity via epigenetic regulation of telomerase reverse transcriptase in non-small cell lung cancer cells. J Cell Biochem 112:3044–3053

    CAS  PubMed  Google Scholar 

  • Li DW, Xie SB, Ren Y, Huo LH, Gao JM, Cui DD, Liu M, ZHOU J (2011b) Microtubule-associated deacetylase HDAC6 promotes angiogenesis by regulating cell migration in an EB1-dependent manner. Protein Cell 2:150–160

    CAS  PubMed  Google Scholar 

  • Licciardi PV, Kwa FAA, Ververis K, Di Costanzo N, Balcerczyk A, Tang ML, El-Osta A, Karagiannis TC (2012) Influence of natural and synthetic histone deacetylase inhibitors on chromatin. Antioxid Redox Signal 17:340–354

    CAS  PubMed  Google Scholar 

  • Lin KT, Momparler RL, Rivard GE (1981) High-performance liquid chromatographic analysis of chemical stability of 5-aza-2′-deoxycytidine. J Pharm Sci 70:1228–1232

    CAS  PubMed  Google Scholar 

  • Lin K, Wang Y, Chen C, Ho C, Su W, Jou Y (2012a) HDAC inhibitors augmented cell migration and metastasis through induction of PKCs leading to identification of low toxicity modalities for combination cancer therapy. Clin Cancer Res 18:4691–4701

    CAS  PubMed  Google Scholar 

  • Lin Y-Y, Kiihl S, Suhail Y, Liu S-Y, Chou Y-H, Kuang Z, Lu J-Y, Khor CN, Lin C-L, Bader JS, Irizarry R, Boeke JD (2012b) Functional dissection of lysine deacetylases reveals that HDAC1 and p300 regulate AMPK. Nature 482:251–255

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lindemann RK, Newbold A, Whitecross KF, Cluse LA, Frew AJ, Ellis L, Williams S, Wiegmans AP, Dear AE, Scott CL, Pellegrini M, Wei A, Richon VM, Marks PA, Lowe SW, Smyth MJ, Johnstone RW (2007) Analysis of the apoptotic and therapeutic activities of histone deacetylase inhibitors by using a mouse model of B cell lymphoma. Proc Natl Acad Sci U S A 104:8071

    CAS  PubMed Central  PubMed  Google Scholar 

  • Luger K, Mader AW (1997) Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389:251

    CAS  PubMed  Google Scholar 

  • Ma Y, Cai S, Lu Q, Lu X, Jiang Q, Zhou J, Zhang C (2008) Inhibition of protein deacetylation by trichostatin A impairs microtubule-kinetochore attachment. Cell Mol Life Sci 65:3100–3109

    CAS  PubMed  Google Scholar 

  • Marks PA (2007) Discovery and development of SAHA as an anticancer agent. Oncogene 26:1351–1356

    CAS  PubMed  Google Scholar 

  • Marks PW (2012) Decitabine for acute myeloid leukemia. Expert Rev Anticancer Ther 12:299–305

    CAS  PubMed  Google Scholar 

  • Martinez-Balbas MA, Bannister AJ, Martin K, Haus-Seuffert P, Meisterernst M, Kouzarides T (1998) The acetyltransferase activity of CBP stimulates transcription. EMBO J 17:2886–2893

    CAS  PubMed Central  PubMed  Google Scholar 

  • Matsushita H, Scaglioni PP, Bhaumik M, Rego EM, Cai LF, Majid SM, Miyachi H, Kakizuka A, Miller WH, Pandolfi PP (2006) In vivo analysis of the role of aberrant histone deacetylase recruitment and RAR alpha blockade in the pathogenesis of acute promyelocytic leukemia. J Exp Med 203:821–828

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mckinsey TA, Zhang CL, Lu J, Olson EN (2000) Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature 408:106–111

    CAS  PubMed  Google Scholar 

  • Mercurio C, Minucci S, Pelicci PG (2010) Histone deacetylases and epigenetic therapies of hematological malignancies. Pharmacol Res 62:18–34

    CAS  PubMed  Google Scholar 

  • Miriam KK, Mark AB (2010) Review: a mobile threat to genome stability: the impact of non-LTR retrotransposons upon the human genome. Semin Cancer Biol 20:211–221

    Google Scholar 

  • Mombelli M, Lugrin J, Rubino I, Chanson AL, Giddey M, Calandra T, Roger T (2011) Histone deacetylase inhibitors impair antibacterial defenses of macrophages. J Infect Dis 204:1367–1374

    CAS  PubMed  Google Scholar 

  • Momparler RL, Momparler LF, Samson J (1984) Comparison of the antileukemic activity of 5-AZA-2′-deoxycytidine, 1-beta-D-arabinofuranosylcytosine and 5-azacytidine against L1210 leukemia. Leuk Res 8:1043–1049

    CAS  PubMed  Google Scholar 

  • Monneret C (2005) Histone deacetylase inhibitors. Eur J Med Chem 40:1–13

    CAS  PubMed  Google Scholar 

  • Muotri AR, Marchetto MC, Coufal NG, Oefner R, Yeo G, Nakashima K, Gage FH (2010) L1 retrotransposition in neurons is modulated by MeCP2. Nature 468:443–446

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nebbioso A, Clarke N, Voltz E, Germain E, Ambrosino C, Bontempo P, Alvarez R, Schiavone EM, Ferrara F, Bresciani F, Weisz A, De Lera AR, Gronemeyer H, Altucci L (2005) Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells. Nat Med 11:77–84

    CAS  PubMed  Google Scholar 

  • Newbold A, Lindemann RK, Cluse LA, Whitecross KF, Dear AE, Johnstone RW (2008) Characterisation of the novel apoptotic and therapeutic activities of the histone deacetylase inhibitor romidepsin. Mol Cancer Ther 7:1066–1079

    CAS  PubMed  Google Scholar 

  • Ng SS, Yue WW, Oppermann U, Klose RJ (2009) Dynamic protein methylation in chromatin biology. Cell Mol Life Sci 66:407–422

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nordentoft I, Jorgensen P (2003) The acetyltransferase 60 kDa trans-acting regulatory protein of HIV type 1-interacting protein (Tip60) interacts with the translocation E26 transforming-specific leukaemia gene (TEL) and functions as a transcriptional co-repressor. Biochem J 374:165–173

    CAS  PubMed Central  PubMed  Google Scholar 

  • Notari RE, Deyoung JL (1975) Kinetics and mechanisms of degradation of the antileukemic agent 5-azacytidine in aqueous solutions. J Pharm Sci 64:1148–1157

    CAS  PubMed  Google Scholar 

  • Notbohm H, Hollandt H, Meissner J, Harbers E (1979) Low angle X-ray scattering studies of chromatin in different solvents; analysis by comparison with computer-simulated scattering curves. Int J Biol Macromol 1:180–184

    CAS  Google Scholar 

  • Oberoi J, Fairall L, Watson PJ, Yang JC, Czimmerer Z, Kampmann T, Goult BT, Greenwood JA, Gooch JT, Kallenberger BC, Nagy L, Neuhaus D, Schwabe JW (2011) Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery. Nat Struct Mol Biol 18:177–184

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pal S, Sif S (2007) Interplay between chromatin remodelers and protein arginine methyltransferases. J Cell Physiol 213:306–315

    CAS  PubMed  Google Scholar 

  • Patrick I, Eleftherios PS, Michael S, Daniel F, André F (2011) Endometriosis: inhibition of transcription, expression, and secretion of the vascular epithelial growth factor in human epithelial endometriotic cells by romidepsin. Fertil Steril 95:1579–1583

    Google Scholar 

  • Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM (2000) A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol 10:886–895

    CAS  PubMed  Google Scholar 

  • Peart MJ, Tainton KM, Ruefli AA, Dear AE, Sedelies KA, O’reilly LA, Waterhouse NJ, Trapani JA, Johnstone RW (2003) Novel mechanisms of apoptosis induced by histone deacetylase inhibitors. Cancer Res 63:4460–4471

    CAS  PubMed  Google Scholar 

  • Peart MJ, Smyth GK, Van Laar RK, Bowtell DD, Richon VM, Marks PA, Holloway AJ, Johnstone RW (2005) Identification and functional significance of genes regulated by structurally different histone deacetylase inhibitors. Proc Natl Acad Sci U S A 102:3697–3702

    CAS  PubMed Central  PubMed  Google Scholar 

  • Peng C, Lu Z, Xie Z, Cheng Z, Chen Y, Tan M, Luo H, Zhang Y, He W, Yang K, Zwaans BM, Tishkoff D, Ho L, Lombard D, He TC, Dai J, Verdin E, Ye Y, Zhao Y (2011) The first identification of lysine malonylation substrates and its regulatory enzyme. Mol Cell Proteomics 10(12):M111

    PubMed Central  PubMed  Google Scholar 

  • Piekarz RL, Frye R, Turner M, Wright JJ, Allen SL, Kirschbaum MH, Zain J, Prince HM, Leonard JP, Geskin LJ, Reeder C, Joske D, Figg WD, Gardner ER, Steinberg SM, Jaffe ES, Stetler-Stevenson M, Lade S, Fojo AT, Bates SE (2009) Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27:5410–5417

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A (1996) Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem 271:12687–12690

    CAS  PubMed  Google Scholar 

  • Qian DZ, Kachhap SK, Collis SJ, Verheul HMW, Carducci MA, Atadja P, Pili R (2006) Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1α. Cancer Res 66:8814–8821

    CAS  PubMed  Google Scholar 

  • Qian-Ying L, Da-Wei C, Li-Ping X, Rong-Qing Z, Hong-Zhong W (2012) Decitabine, independent of apoptosis, exerts its cytotoxic effects on cell growth in melanoma cells. Environ Toxicol Pharmacol 32:423–429

    Google Scholar 

  • Ramirez J, Dege C, Kutateladze TG, Hagman J (2012) MBD2 and multiple domains of CHD4 are required for transcriptional repression by Mi-2/NuRD complexes. Mol Cell Biol 32:5078–5088

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rangwala S, Duvic M, Chunlei Z (2012) Trends in the treatment of cutaneous T-cell lymphoma—critical evaluation and perspectives on vorinostat. Blood Lymph Cancer Targets Ther 2:17–27

    CAS  Google Scholar 

  • Rea S, Eisenhaber F, O’Carroll D, Strahl BD, Sun ZW, Schmid M, Opravil S, Mechtler K, Ponting CP, Allis CD, Jenuwein T (2000) Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406:593

    CAS  PubMed  Google Scholar 

  • Reik W, Dean W, Walter JR (2001) Epigenetic reprogramming in mammalian development. Science 1089

    Google Scholar 

  • Richon VM, Sandhoff TW, Rifkind RA, Marks PA (2000) Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation. Proc Natl Acad Sci U S A 97:10014–10019

    CAS  PubMed Central  PubMed  Google Scholar 

  • Robbins AR, Jablonski SA, Yen TJ, Yoda K, Robey R, Bates SE, Sackett DL (2005) Inhibitors of histone deacetylases alter kinetochore assembly by disrupting pericentromeric heterochromatin. Cell Cycle 4:717–726

    CAS  PubMed  Google Scholar 

  • Rodriguez J, Frigola J, Vendrell E, Risques RA, Fraga MF, Morales C, Moreno V, Esteller M, Capellà G, Ribas M, Peinado MA (2006) Chromosomal instability correlates with genome-wide DNA demethylation in human primary colorectal cancers. Cancer Res 66:8462–8468

    CAS  PubMed  Google Scholar 

  • Rosato RR, Grant S (2005) Histone deacetylase inhibitors: insights into mechanisms of lethality. Expert Opin Ther Targets 9:809–824

    CAS  PubMed  Google Scholar 

  • Roth SY, Denu JM, Allis CD (2001) Histone acetyltransferases. Annu Rev Biochem 70:81

    CAS  PubMed  Google Scholar 

  • Roy AF (2000) Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun 273:793–798

    Google Scholar 

  • Sapountzi V, Coté J (2010) MYST-family histone acetyltransferases: beyond chromatin. Cell Mol Life Sci 68:1147–1156

    PubMed  Google Scholar 

  • Sarfstein R, Bruchim I, Fishman A, Werner H (2010) The mechanism of action of the histone deacetylase inhibitor vorinostat involves interaction with the insulin-like growth factor signaling pathway. PLoS One 6:1–12

    Google Scholar 

  • Sato A (2012) Vorinostat approved in Japan for treatment of cutaneous T-cell lymphomas: status and prospects. Onco Targets Ther 5:67–75

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sauve AA, Wolberger C, Schramm VL, Boeke JD (2006) The biochemistry of sirtuins. Annu Rev Biochem 75:435–465

    CAS  PubMed  Google Scholar 

  • Schmudde M, Braun A, Pende D, Sonnemann J, Klier U, Beck JF, Moretta L, Broker BM (2008) Histone deacetylase inhibitors sensitize tumour cells for cytotoxic effects of natural killer cells. Cancer Lett 272:110–121

    CAS  PubMed  Google Scholar 

  • Schmudde M, Friebe E, Sonnemann J, Beck JF, Broker BM (2010) Histone deacetylase inhibitors prevent activation of tumour-reactive NK cells and T cells but do not interfere with their cytolytic effector functions. Cancer Lett 295:173–181

    CAS  PubMed  Google Scholar 

  • Schrump DS (2009) Cytotoxicity mediated by histone deacetylase inhibitors in cancer cells: mechanisms and potential clinical implications. Clin Cancer Res 15:3947–3957

    CAS  PubMed  Google Scholar 

  • Seigneurin-Berny D, Verdel A, Curtet S, Lemercier C, Garin J, Rousseaux S, Khochbin S (2001) Identification of components of the murine histone deacetylase 6 complex: link between acetylation and ubiquitination signaling pathways. Mol Cell Biol 21:8035–8044

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shao L-E, Diccianni MB, Tanaka T, Gribi R, Yu AL, Pullen JD, Camitta BM, Yu J (2001) Thioredoxin expression in primary T-cell acute lymphoblastic leukemia and its therapeutic implication. Cancer Res 61:7333–7338

    CAS  PubMed  Google Scholar 

  • Sharp AJ, Stathaki E, Migliavacca E, Brahmachary M, Montgomery SB, Dupre Y, Antonarakis SE (2011) DNA methylation profiles of human active and inactive X chromosomes. Genome Res 21:1592–1600

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Shia WJ, Okumura AJ, Yan M, Sarkeshik A, Lo MC, Matsuura S, Komeno Y, Zhao X, Nimer SD, Yates JR III, Zhang DE (2012) PRMT1 interacts with AML1-ETO to promote its transcriptional activation and progenitor cell proliferative potential. Blood 119:4953–4962

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shin DY, Kim GY, Kim CG, Kim WJ, Kang HS, Choi YH (2012) Anti-invasive effects of decitabine, a DNA methyltransferase inhibitor, through tightening of tight junctions and inhibition of matrix metalloproteinase activities in AGS human gastric carcinoma cells. Oncol Rep 28:1043–1050

    CAS  PubMed  Google Scholar 

  • Silverman LR, Holland JF, Weinberg RS, Alter BP, Davis RB, Ellison RR, Demakos EP, Cornell CJ Jr, Carey RW, Schiffer C (1993) Effects of treatment with 5-azacytidine on the in vivo and in vitro hematopoiesis in patients with myelodysplastic syndromes. Leukemia 7(Suppl 1):21–9

    PubMed  Google Scholar 

  • Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R, Stone RM, Nelson D, Powell BL, DeCastro CM, Ellerton J, Larson RA, Schiffer CA, Holland JF (2002) Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 20:2429–2440

    CAS  PubMed  Google Scholar 

  • Smallwood SA, Kelsey G (2011) De novo DNA methylation: a germ cell perspective. Trends Genet 28:33–42

    PubMed  Google Scholar 

  • Smit AFA, Riggs AD (1996) Tiggers and other DNA transposon fossils in the human genome. Proc Natl Acad Sci U S A 93(4):1443–8 [Online, Accessed 12 Dec 2012]

    CAS  PubMed Central  PubMed  Google Scholar 

  • Smith ZD, Chan MM, Mikkelsen TS, Gu H, Gnirke A, Regev A, Meissner A (2012) A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature 484:339–344

    CAS  PubMed Central  PubMed  Google Scholar 

  • Smrzka OW, Faé I, Stöger R, Kurzbauer R, Fischer GF, Henn T, Weith A, Barlow DP (1995) Conservation of a maternal-specific methylation signal at the human Igf2r locus. Hum Mol Genet 4:1945–1952

    CAS  PubMed  Google Scholar 

  • Matias S, Fabio S, Arantxa G, Gianmaria F, Mauro R, Oronza AB, Isabella P, Piergiuseppe P, Luciano Di C, Saverio M (2013) The DNA demethylating agent decitabine activates the TRAIL pathway and induces apoptosis in acute myeloid leukemia. Biochim Biophys Acta 1832:114–120

    Google Scholar 

  • Steinhoff C, Schulz WA (2004) Transcriptional regulation of the human LINE-1 retrotransposon L1.2B. Mol Genet Genomics 270:394–402

    Google Scholar 

  • Sterner D, Berger S (2000) Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev 64:435–461

    CAS  PubMed Central  PubMed  Google Scholar 

  • Strathdee G, Mackean MJ, Illand M, Brown R (1999) A role for methylation of the hMLH1 promoter in loss of hMLH1 expression and drug resistance in ovarian cancer. Oncogene 18:2335–2341

    CAS  PubMed  Google Scholar 

  • Stunkel W, Campbell RM (2011) Sirtuin 1 (SIRT1): the misunderstood HDAC. J Biomol Screen 16:1153–1169

    CAS  PubMed  Google Scholar 

  • Szerlong HJ, Hansen JC (2011) Nucleosome distribution and linker DNA: connecting nuclear function to dynamic chromatin structure. Biochem Cell Biol 89:24–34

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tachimori A, Yamada N, Sakate Y, Yashiro M, Maeda K, Ohira M, Nishino H, Hirakawa K (2005) Up regulation of ICAM-1 gene expression inhibits tumour growth and liver metastasis in colorectal carcinoma. Eur J Cancer 41:1802–1810

    CAS  PubMed  Google Scholar 

  • Takai D, Jones PA (2002) Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci U S A 3740

    Google Scholar 

  • Tickenbrock L, Klein HU, Trento C, Hascher A, Göllner S, Bäumer N, Kuss R, Agrawal S, Bug G, Serve H, Thiede C, Ehninger G, Stadt UZ, McClelland M, Wang Y, Becker A, Koschmieder S, Berdel WE, Dugas M, Müller-Tidow C (2011) Increased HDAC1 deposition at hematopoietic promoters in AML and its association with patient survival. Leuk Res 35:620–625

    CAS  PubMed  Google Scholar 

  • Tiffon C, Adams J, van der Fits L, Wen S, Townsend P, Ganesan A, Hodges E, Vermeer M, Packham G (2011) The histone deacetylase inhibitors vorinostat and romidepsin downmodulate IL-10 expression in cutaneous T-cell lymphoma cells. Br J Pharmacol 162:1590–1602

    CAS  PubMed Central  PubMed  Google Scholar 

  • Turner BM (2000) Histone acetylation and an epigenetic code. Bioessays 22(9):836–45 [Online, Accessed 11 Dec 2012]

    CAS  PubMed  Google Scholar 

  • Turner BM (2005) Reading signals on the nucleosome with a new nomenclature for modified histones. Nat Struct Mol Biol 12:110–112

    CAS  PubMed  Google Scholar 

  • Ungerstedt JS, Sowa Y, Xu WS, Shao Y, Dokmanovic M, Perez G, Ngo L, Holmgren A, Jiang X, Marks PA (2005) Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors. Proc Natl Acad Sci U S A 102:673–678

    CAS  PubMed Central  PubMed  Google Scholar 

  • Vega RB, Matsuda K, Oh J, Barbosa AC, Yang X, Meadows E, McAnally J, Pomajzl C, Shelton JM, Richardson JA, Karsenty G, Olson EN (2004) Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell 119:555–566

    CAS  PubMed  Google Scholar 

  • Verdin E, Dequiedt F, Kasler HG (2003) Class II histone deacetylases: versatile regulators. Trends Genet 19:286–293

    CAS  PubMed  Google Scholar 

  • Völkel P, Angrand P-O (2007) The control of histone lysine methylation in epigenetic regulation. Biochimie 89:1–20

    PubMed  Google Scholar 

  • Wang Z, Zang C, Cui K, Schones DE, Barski A, Peng W, Zhao K (2009) Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes. Cell 138:1019–1031

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang RR, Li Q, Helfer CM, Jiao J, You JX (2012) Bromodomain protein Brd4 associated with acetylated chromatin is important for maintenance of higher-order chromatin structure. J Biol Chem 287:10738–10752

    CAS  PubMed Central  PubMed  Google Scholar 

  • Weber M, Hellmann I, Stadler MB, Ramos L, Paabo S, Rebhan M, Schubeler D (2007) Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet 39:457–466

    CAS  PubMed  Google Scholar 

  • Weichert W (2009) HDAC expression and clinical prognosis in human malignancies. Cancer Lett 280:168–176

    CAS  PubMed  Google Scholar 

  • Weichert W, Röske A, Gekeler V, Beckers T, Stephan C, Jung K, Fritzsche FR, Niesporek S, Denkert C, Dietel M, Kristiansen G (2008a) Histone deacetylases 1, 2 and 3 are highly expressed in prostate cancer and HDAC2 expression is associated with shorter PSA relapse time after radical prostatectomy. Br J Cancer 98:604–610

    CAS  PubMed Central  PubMed  Google Scholar 

  • Weichert W, Röske A, Niesporek S, Noske A, Buckendahl AC, Dietel M, Gekeler V, Boehm M, Beckers T, Denkert C (2008b) Class I histone deacetylase expression has independent prognostic impact in human colorectal cancer: specific role of class I histone deacetylases in vitro and in vivo. Clin Cancer Res 14:1669–1677

    CAS  PubMed  Google Scholar 

  • Williams SP, Athey BD, Muglia LJ, Schappe RS, Gough AH, Langmore JP (1986) Chromatin fibers are left-handed double helices with diameter and mass per unit length that depend on linker length. Biophys J 49:233–248

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wilson AJ, Byun DS, Popova N, Murray LB, L’Italien K, Sowa Y, Arango D, Velcich A, Augenlicht LH, Mariadason JM (2006) Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer. J Biol Chem 281:13548–13558

    CAS  PubMed  Google Scholar 

  • Wilson AS, Power BE, Molloy PL (2007) DNA hypomethylation and human diseases. Biochim Biophys Acta 1775:138–162

    CAS  PubMed  Google Scholar 

  • Witt O, Deubzer HE, Milde T, Oehme I (2009) HDAC family: what are the cancer relevant targets? Cancer Lett 277

    Google Scholar 

  • Wolf SS (2009) The protein arginine methyltransferase family: an update about function, new perspectives and the physiological role in humans. Cell Mol Life Sci 66:2109–2121

    CAS  PubMed  Google Scholar 

  • Wolfson NA, Pitcairn CA, Fierke CA (2013) HDAC8 Substrates: histones and beyond. Biopolymers 99:112–126

    CAS  PubMed Central  PubMed  Google Scholar 

  • Woodcock C, Skoultchi A, Fan Y (2006) Role of linker histone in chromatin structure and function: H1 stoichiometry and nucleosome repeat length. Chromosome Res 14:17–25

    CAS  PubMed  Google Scholar 

  • Wu P, Tian Y, Chen G, Wang B, Gui L, Xi L, Ma X, Fang Y, Zhu T, Wang D, Meng L, Xu G, Wang S, Ma D, Zhou J (2010) Ubiquitin B: an essential mediator of trichostatin A-induced tumor-selective killing in human cancer cells. Cell Death Differ 17:109–118

    CAS  PubMed  Google Scholar 

  • Wu HC, Delgado-Cruzata L, Flom JD, Perrin M, Liao Y, Ferris JS, Santella RM, Terry MB (2012) Repetitive element DNA methylation levels in white blood cell DNA from sisters discordant for breast cancer from the New York site of the Breast Cancer Family Registry. Carcinogenesis 33:1946–1952

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xiaodong C, Collins RE, Xing Z (2005) Structural and sequence motifs of protein (histone) methylation enzymes. Annu Rev Biophys Biomol Struct 34:267–294

    Google Scholar 

  • Xie HJ, Noh JH, Kim JK, Jung KH, Eun JW, Bae HJ, Kim MG, Chang YG, Lee JY, Park H, Nam SW (2012) HDAC1 inactivation induces mitotic defect and caspase-independent autophagic cell death in liver cancer. PLoS One 7:e34265–e34265

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xu W, Ngo L, Perez G, Dokmanovic M, Marks PA (2006) Intrinsic apoptotic and thioredoxin pathways in human prostate cancer cell response to histone deacetylase inhibitor. Proc Natl Acad Sci U S A 103:15540–15545

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xu WS, Parmigiani RB, Marks PA (2007) Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene 26:5541–52

    CAS  PubMed  Google Scholar 

  • Yang XJ (2004) The diverse superfamily of lysine acetyltransferases and their roles in leukemia and other diseases. Nucleic Acids Res 32:959–976

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yang X-J, Seto E (2008) The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat Rev Mol Cell Biol 9:206–218

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yu F, Zingler N, Schumann G, Stratling WH (2001) Methyl-CpG-binding protein 2 represses LINE-1 expression and retrotransposition but not Alu transcription. Nucleic Acids Res 29:4493–4501

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yuan H, Marmorstein R (2012) Structural basis for sirtuin activity and inhibition. J Biol Chem 287:42428–42435

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang X, Bruice TC (2008) Enzymatic mechanism and product specificity of SET-domain protein lysine methyltransferases. Proc Natl Acad Sci U S A 105:5728–5732

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang CL, Mckinsey TA, Lu JR, Olson EN (2001) Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor. J Biol Chem 276:35–39

    CAS  PubMed  Google Scholar 

  • Zhang X, Zhang Z, Chen G, Zhao M, Wang D, Zhang X, Du Z, Xu Y, Yu X (2010) FK228 induces mitotic catastrophe in A549 cells by mistargeting chromosomal passenger complex localization through changing centromeric H3K9 hypoacetylation. Acta Biochim Biophys Sin (Shanghai) 42:677–687

    CAS  Google Scholar 

  • Zhu P, Martin E, Mengwasser J, Schlag P, Janssen KP, Göttlicher M (2004) Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis. Cancer Cell 5:455–463

    CAS  PubMed  Google Scholar 

  • Ziemba A, Hayes E, Freeman BB III, Tao Y, Pizzorno G (2011) Development of an oral form of azacytidine: 2′3′25′ triacetyl-5-azacytidine. Chemother Res Pract 2011:965826

    PubMed Central  PubMed  Google Scholar 

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  1. Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, 75 Commercial Road, Melbourne, VIC, Australia

    Claire Westerland & Tom C. Karagiannis

  2. Department of Pathology, The University of Melbourne, Parkville, VIC, Australia

    Tom C. Karagiannis

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  1. Department of Surgery Molecular cardiology and Angiogenesis, University of Connecticut School of Medicine, Farmington, Connecticut, USA

    Nilanjana Maulik

  2. Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia

    Tom Karagiannis

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Westerland, C., Karagiannis, T.C. (2014). An Overview of Epigenetic Mechanisms in Health and Disease. In: Maulik, N., Karagiannis, T. (eds) Molecular mechanisms and physiology of disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0706-9_3

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