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HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention

Oncogene volume 26, pages 5310–5318 (2007)Cite this article

Abstract

Acetylation of the ɛ-amino group of a lysine residue was first discovered with histones in 1968, but the responsible enzymes, histone acetyltransferases and deacetylases, were not identified until the mid-1990s. In the past decade, knowledge about this modification has exploded, with targets rapidly expanding from histones to transcription factors and other nuclear proteins, and then to cytoskeleton, metabolic enzymes, and signaling regulators in the cytoplasm. Thus, protein lysine acetylation has emerged as a major post-translational modification to rival phosphorylation. In this issue of Oncogene, 19 articles review various aspects of the enzymes governing lysine acetylation, especially about their intimate links to cancer. To introduce the articles, we highlight here four central themes: (i) multisubunit enzymatic complexes; (ii) non-histone substrates in diverse cellular processes; (iii) interplay of lysine acetylation with other regulatory mechanisms, such as noncoding RNA-mediated gene silencing and activation; and (iv) novel therapeutic strategies and preventive measures to combat cancer and other human diseases.

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References

  • Adams CC, Workman JL . (1993). Nucleosome displacement in transcription. Cell 72: 305–308.

    CAS  PubMed  Google Scholar 

  • Ahn SH, Diaz RL, Grunstein M, Allis CD . (2006). Histone H2B deacetylation at lysine 11 is required for yeast apoptosis induced by phosphorylation of H2B at serine 10. Mol Cell 24: 211–220.

    CAS  PubMed  Google Scholar 

  • Allard S, Utley RT, Savard J, Clarke A, Grant P, Brandl CJ et al. (1999). NuA4, an essential transcription adaptor/histone H4 acetyltransferase complex containing Esa1p and the ATM-related cofactor Tra1p. EMBO J 18: 5108–5119.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Aufsatz W, Stoiber T, Rakic B, Naumann K . (2007). Arabidopsis histone deacetylase 6: a green link to RNA silencing. Oncogene 26: 5477–5488.

    CAS  PubMed  Google Scholar 

  • Avvakumov N, Côté J . (2007). The MYST family of histone acetyltransferases and their intimate links to cancer. Oncogene 26: 5395–5407.

    CAS  PubMed  Google Scholar 

  • Baker SP, Grant PA . (2007). The SAGA continues: expanding the cellular role of a transcriptional co-activator complex. Oncogene 26: 5329–5340.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Balasubramanyam K, Varier RA, Altaf M, Swaminathan V, Siddappa NB, Ranga U et al. (2004). Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J Biol Chem 279: 51163–51171.

    CAS  PubMed  Google Scholar 

  • Bannister AJ, Kouzarides T . (1996). The CBP co-activator is a histone acetyltransferase. Nature 384: 641–643.

    CAS  PubMed  Google Scholar 

  • Becker PB . (1994). The establishment of active promoters in chromatin. Bioessays 16: 541–547.

    CAS  PubMed  Google Scholar 

  • Belfield JL, Whittaker C, Cader MZ, Chawla S . (2006). Differential effects of Ca2+ and cAMP on transcription mediated by MEF2D and cAMP-response element-binding protein in hippocampal neurons. J Biol Chem 281: 27724–27732.

    CAS  PubMed  Google Scholar 

  • Berdeaux R, Goebel N, Banaszynski L, Takemori H, Wandless T, Shelton GD et al. (2007). SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes. Nat Med 13: 597–603.

    CAS  PubMed  Google Scholar 

  • Blander G, Guarente L . (2004). The Sir2 family of protein deacetylases. Annu Rev Biochem 73: 417–435.

    CAS  PubMed  Google Scholar 

  • Borrow J, Stanton Jr VP, Andresen JM, Becher R, Behm FG, Chaganti RS et al. (1996). The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Nat Genet 14: 33–41.

    CAS  PubMed  Google Scholar 

  • Boyault C, Sadoul K, Pabion M, Khochbin S . (2007). HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination. Oncogene 26: 5468–5476.

    CAS  PubMed  Google Scholar 

  • Brownell JE, Allis CD . (1995). An activity gel assay detects a single, catalytically active histone acetyltransferase subunit in Tetrahymena macronuclei. Proc Natl Acad Sci USA 92: 6364–6368.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brownell JE, Zhou J, Ranalli T, Kobayashi R, Edmondson DG, Roth SY et al. (1996). Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84: 843–851.

    CAS  PubMed  Google Scholar 

  • Brush MH, Guardiola A, Connor JH, Yao TP, Shenolikar S . (2004). Deactylase inhibitors disrupt cellular complexes containing protein phosphatases and deacetylases. J Biol Chem 279: 7685–7691.

    CAS  PubMed  Google Scholar 

  • Candido EP, Reeves R, Davie JR . (1978). Sodium butyrate inhibits histone deacetylation in cultured cells. Cell 14: 105–113.

    CAS  PubMed  Google Scholar 

  • Canettieri G, Morantte I, Guzman E, Asahara H, Herzig S, Anderson SD et al. (2003). Attenuation of a phosphorylation-dependent activator by an HDAC–PP1 complex. Nat Struct Biol 10: 175–181.

    CAS  PubMed  Google Scholar 

  • Chen Y, Sprung R, Tang Y, Ball H, Sangras B, Kim S et al. (2007). Lysine propionylation and butyrylation are novel post-translational modifications in histones. Mol Cell Proteomics 6: 812–819.

    CAS  PubMed  Google Scholar 

  • Chinenov Y . (2002). A second catalytic domain in the Elp3 histone acetyltransferases: a candidate for histone demethylase activity? Trends Biochem Sci 27: 115–117.

    CAS  PubMed  Google Scholar 

  • Cohen T, Yao TP . (2004). AcK-knowledge reversible acetylation. Sci STKE, pe42.

    Google Scholar 

  • Collins SR, Miller KM, Maas NL, Roguev A, Fillingham J, Chu CS et al. (2007). Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map. Nature 446: 806–810.

    CAS  PubMed  Google Scholar 

  • Cress WD, Seto E. (2000). Histone deacetylases, transcriptional control, and cancer. J Cell Physiol 184: 1–16.

    CAS  PubMed  Google Scholar 

  • Denslow SA, Wade PA . (2007). The human Mi-2/NuRD complex and gene regulation. Oncogene 26: 5433–5438.

    CAS  PubMed  Google Scholar 

  • Dequiedt F, Kasler H, Fischle W, Kiermer V, Weinstein M, Herndier BG et al. (2003). HDAC7, a thymus-specific class II histone deacetylase, regulates Nur77 transcription and TCR-mediated apoptosis. Immunity 18: 687–698.

    CAS  PubMed  Google Scholar 

  • Doyon Y, Cote J . (2004). The highly conserved and multifunctional NuA4 HAT complex. Curr Opin Genet Dev 14: 147–154.

    CAS  PubMed  Google Scholar 

  • Driscoll R, Hudson A, Jackson SP . (2007). Yeast Rtt109 promotes genome stability by acetylating histone H3 on lysine 56. Science 315: 649–652.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Druesne N, Pagniez A, Mayeur C, Thomas M, Cherbuy C, Duee PH et al. (2004). Diallyl disulfide (DADS) increases histone acetylation and p21(waf1/cip1) expression in human colon tumor cell lines. Carcinogenesis 25: 1227–1236.

    CAS  PubMed  Google Scholar 

  • Earley K, Lawrence RJ, Pontes O, Reuther R, Enciso AJ, Silva M et al. (2006). Erasure of histone acetylation by Arabidopsis HDA6 mediates large-scale gene silencing in nucleolar dominance. Genes Dev 20: 1283–1293.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gershey EL, Vidali G, Allfrey VG . (1968). Chemical studies of histone acetylation. The occurrence of epsilon-N-acetyllysine in the f2a1 histone. J Biol Chem 243: 5018–5022.

    CAS  PubMed  Google Scholar 

  • Glozak MA, Seto E . (2007). Histone deacetylases and cancer. Oncogene 26: 5420–5432.

    CAS  PubMed  Google Scholar 

  • Goldberg AD, Allis CD, Bernstein E . (2007). Epigenetics: a landscape takes shape. Cell 128: 635–638.

    CAS  PubMed  Google Scholar 

  • Goodman RH, Smolik S . (2000). CBP/p300 in cell growth, transformation, and development. Genes Dev 14: 1553–1577.

    CAS  PubMed  Google Scholar 

  • Grant PA, Schieltz D, Pray-Grant MG, Yates JR, Workman JL . (1998). The ATM-related cofactor Tra1 is a component of the purified SAGA complex. Mol Cell 2: 863–867.

    CAS  PubMed  Google Scholar 

  • Grégoire S, Xiao L, Nie J, Xu M, Wong J, Seto E et al. (2007). Histone deacetylase 3 interacts and deacetylates MEF2 transcription factors. Mol Cell Biol 27: 1280–1295.

    PubMed  Google Scholar 

  • Gregoretti IV, Lee YM, Goodson HV . (2004). Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J Mol Biol 338: 17–31.

    CAS  PubMed  Google Scholar 

  • Grossman SR, Deato ME, Brignone C, Chan HM, Kung AL, Tagami H et al. (2003). Polyubiquitination of p53 by a ubiquitin ligase activity of p300. Science 300: 342–344.

    CAS  PubMed  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 

  • Gu W, Roeder RG . (1997). Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 90: 595–606.

    CAS  PubMed  Google Scholar 

  • Hallows WC, Lee S, Denu JM . (2006). Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc Natl Acad Sci USA 103: 10230–10235.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Han J, Zhou H, Horazdovsky B, Zhang K, Xu RM, Zhang Z . (2007). Rtt109 acetylates histone H3 lysine 56 and functions in DNA replication. Science 315: 653–655.

    CAS  PubMed  Google Scholar 

  • Hansen JC, Ausio J . (1992). Chromatin dynamics and the modulation of genetic activity. Trends Biochem Sci 17: 187–191.

    CAS  PubMed  Google Scholar 

  • Hodawadekar SC, Marmorstein R . (2007). Chemistry of acetyl transfer by histone modifying enzymes: structure, mechanism and implications for effector design. Oncogene 26: 5528–5540.

    CAS  PubMed  Google Scholar 

  • Humphrey GW, Wang Y, Russanova VR, Hirai T, Qin J, Nakatani Y et al. (2001). Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1. J Biol Chem 276: 6812–6824.

    Google Scholar 

  • Ikura T, Ogryzko VV, Grigoriev M, Groisman R, Wang J, Horikoshi M et al. (2000). Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis. Cell 102: 463–473.

    CAS  PubMed  Google Scholar 

  • Imhof A, Yang X-J, Ogryzko VV, Nakatani Y, Wolffe AP, Ge H . (1997). Acetylation of general transcription factors by histone acetyltransferases. Curr Biol 7: 689–692.

    CAS  PubMed  Google Scholar 

  • Ito K, Ito M, Elliott WM, Cosio B, Caramori G, Kon OM et al. (2005). Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med 352: 1967–1976.

    CAS  PubMed  Google Scholar 

  • Ivanov D, Schleiffer A, Eisenhaber F, Mechtler K, Haering CH, Nasmyth K . (2002). Eco1 is a novel acetyltransferase that can acetylate proteins involved in cohesion. Curr Biol 12: 323–328.

    CAS  PubMed  Google Scholar 

  • Iwabata H, Yoshida M, Komatsu Y . (2005). Proteomic analysis of organ-specific post-translational lysine-acetylation and -methylation in mice by use of anti-acetyllysine and -methyllysine mouse monoclonal antibodies. Proteomics 5: 4653–4664.

    CAS  PubMed  Google Scholar 

  • Iwata A, Riley BE, Johnston JA, Kopito RR . (2005). HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin. J Biol Chem 280: 40282–40292.

    CAS  PubMed  Google Scholar 

  • Jenuwein T, Allis CD . (2001). Translating the histone code. Science 293: 1074–1080.

    CAS  PubMed  Google Scholar 

  • Kamine J, Elangovan B, Subramanian T, Coleman D, Chinnadurai G . (1996). Identification of a cellular protein that specifically interacts with the essential cysteine region of the HIV-1 Tat transactivator. Virology 216: 357–366.

    CAS  PubMed  Google Scholar 

  • Karagianni P, Wong J . (2007). HDAC3: taking the SMRT-N-CoRrect road to repression. Oncogene 26: 5439–5449.

    CAS  PubMed  Google Scholar 

  • Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao TP . (2003). The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 115: 727–738.

    CAS  PubMed  Google Scholar 

  • Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J et al. (2006). Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell 23: 607–618.

    CAS  PubMed  Google Scholar 

  • Kleff S, Andrulis ED, Anderson CW, Sternglanz R . (1995). Identification of a gene encoding a yeast histone H4 acetyltransferase. J Biol Chem 270: 24674–24677.

    CAS  PubMed  Google Scholar 

  • Koo SH, Flechner L, Qi L, Zhang X, Screaton RA, Jeffries S et al. (2005). The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature 437: 1109–1111.

    CAS  PubMed  Google Scholar 

  • Kouzarides T . (2000). Acetylation: a regulatory modification to rival phosphorylation? EMBO J 19: 1176–1179.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Lafon A, Chang CS, Scott EM, Jacobson SJ, Pillus L . (2007). MYST opportunities for growth control: yeast genes illuminate human cancer gene functions. Oncogene 26: 5373–5384.

    CAS  PubMed  Google Scholar 

  • Lanz RB, McKenna NJ, Onate SA, Albrecht U, Wong J, Tsai SY et al. (1999). A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell 97: 17–27.

    CAS  PubMed  Google Scholar 

  • Lee KK, Workman JL . (2007). Histone acetyltransferase complexes: one size doesn't fit all. Nat Rev Mol Cell Biol 8: 284–295.

    CAS  PubMed  Google Scholar 

  • Lee MG, Wynder C, Cooch N, Shiekhattar R . (2005). An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation. Nature 437: 432–435.

    CAS  PubMed  Google Scholar 

  • L'Hernault SW, Rosenbaum JL . (1985). Chlamydomonas alpha-tubulin is posttranslationally modified by acetylation on the epsilon-amino group of a lysine. Biochemistry 24: 473–478.

    CAS  PubMed  Google Scholar 

  • Li B, Carey M, Workman JL . (2007). The role of chromatin during transcription. Cell 128: 707–719.

    CAS  PubMed  Google Scholar 

  • Li Y, Kao GD, Garcia BA, Shabanowitz J, Hunt DF, Qin J et al. (2006). A novel histone deacetylase pathway regulates mitosis by modulating Aurora B kinase activity. Genes Dev 20: 2566–2579.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lin W, Dent SY . (2006). Functions of histone-modifying enzymes in development. Curr Opin Genet Dev 16: 137–142.

    CAS  PubMed  Google Scholar 

  • Linares LK, Kiernan R, Triboulet R, Chable-Bessia C, Latreille D, Cuvier O et al. (2007). Intrinsic ubiquitination activity of PCAF controls the stability of the oncoprotein Hdm2. Nat Cell Biol 9: 331–338.

    CAS  PubMed  Google Scholar 

  • Liu L, Scolnick DM, Trievel RC, Zhang HB, Marmorstein R, Halazonetis TD et al. (1999). p53 Sites acetylated in vitro by PCAF and p300 are acetylated in vivo in response to DNA damage. Mol Cell Biol 19: 1202–1909.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lucchesi JC, Kelly WG, Panning B . (2005). Chromatin remodeling in dosage compensation. Annu Rev Genet 39: 615–651.

    CAS  PubMed  Google Scholar 

  • Marchion D, Munster P . (2007). Development of histone deacetylase inhibitors for cancer treatment. Expert Rev Anticancer Ther 7: 583–598.

    CAS  PubMed  Google Scholar 

  • Martin M, Kettmann R, Dequiedt F . (2007). Class IIa histone deacetylases: regulating the regulators. Oncogene 26: 5450–5467.

    CAS  PubMed  Google Scholar 

  • McMahon SB, Buskirk HAV, Dugan KA, Copeland TD, Cole MD . (1998). The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins. Cell 94: 363–374.

    CAS  PubMed  Google Scholar 

  • Mejat A, Ramond F, Bassel-Duby R, Khochbin S, Olson EN, Schaeffer L . (2005). Histone deacetylase 9 couples neuronal activity to muscle chromatin acetylation and gene expression. Nat Neurosci 8: 313–321.

    CAS  PubMed  Google Scholar 

  • Minucci S, Pelicci PG . (2006). Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 6: 38–51.

    CAS  PubMed  Google Scholar 

  • Mittal R, Peak-Chew SY, McMahon HT . (2006). Acetylation of MEK2 and I kappa B kinase (IKK) activation loop residues by YopJ inhibits signaling. Proc Natl Acad Sci USA 103: 18574–18579.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mizzen CA, Yang XJ, Kokubo T, Brownell JE, Bannister AJ, Owen-Hughes T et al. (1996). The TAF(II)250 subunit of TFIID has histone acetyltransferase activity. Cell 87: 1261–1270.

    CAS  PubMed  Google Scholar 

  • Mujtaba S, Zeng L, Zhou M-M . (2007). Structure and acetyl-lysine recognition of the bromodomain. Oncogene 26: 5521–5527.

    CAS  PubMed  Google Scholar 

  • Mukherjee S, Keitany G, Li Y, Wang Y, Ball HL, Goldsmith EJ et al. (2006). Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation. Science 312: 1211–1214.

    CAS  PubMed  Google Scholar 

  • Murr R, Vaissière T, Sawan C, Shukla V, Herceg Z . (2007). Orchestration of chromatin-based processes: mind the TRRAP. Oncogene 26: 5358–5372.

    CAS  PubMed  Google Scholar 

  • Myzak MC, Karplus PA, Chung FL, Dashwood RH . (2004). A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase. Cancer Res 64: 5767–5774.

    CAS  PubMed  Google Scholar 

  • Nagy Z, Tora L . (2007). Distinct GCN5/PCAF-containing complexes function as co-activators and are involved in transcription factor and global histone acetylation. Oncogene 26: 5341–5357.

    CAS  PubMed  Google Scholar 

  • Nicolas E, Yamada T, Cam HP, Fitzgerald PC, Kobayashi R, Grewal SI . (2007). Distinct roles of HDAC complexes in promoter silencing, antisense suppression and DNA damage protection. Nat Struct Mol Biol 14: 372–380.

    CAS  PubMed  Google Scholar 

  • Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y . (1996). The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 87: 953–959.

    CAS  PubMed  Google Scholar 

  • Okamoto M, Takemori H, Katoh Y . (2004). Salt-inducible kinase in steroidogenesis and adipogenesis. Trends Endocrinol Metab 15: 21–26.

    CAS  PubMed  Google Scholar 

  • Paranjape SM, Kamakaka RT, Kadonaga JT . (1994). Role of chromatin structure in the regulation of transcription by RNA polymerase II. Annu Rev Biochem 63: 265–297.

    CAS  PubMed  Google Scholar 

  • Parthun MR . (2007). Hat1: the emerging cellular roles of a type B histone acetyltransferase. Oncogene 26: 5319–5328.

    CAS  PubMed  Google Scholar 

  • Parthun MR, Widom J, Gottschling DE . (1996). The major cytoplasmic histone acetyltransferase in yeast: links to chromatin replication and histone metabolism. Cell 87: 85–94.

    CAS  PubMed  Google Scholar 

  • Peterson CL, Tamkun JW . (1995). The SWI–SNF complex: a chromatin remodeling machine? Trends Biochem Sci 20: 143–146.

    CAS  PubMed  Google Scholar 

  • Phillips DM . (1963). The presence of acetyl groups of histones. Biochem J 87: 258–263.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Piperno G, Fuller MT . (1985). Monoclonal antibodies specific for an acetylated form of alpha-tubulin recognize the antigen in cilia and flagella from a variety of organisms. J Cell Biol 101: 2085–2094.

    CAS  PubMed  Google Scholar 

  • Rasheed WK, Johnstone RW, Prince HM . (2007). Histone deacetylase inhibitors in cancer therapy. Expert Opin Investig Drugs 16: 659–678.

    CAS  PubMed  Google Scholar 

  • Rea S, Xouri G, Akhtar A . (2007). Males absent on the first (MOF): from flies to humans. Oncogene 26: 5385–5394.

    CAS  PubMed  Google Scholar 

  • Reifsnyder C, Lowell J, Clarke A, Pillus L . (1996). Yeast SAS silencing genes and human genes associated with AML and HIV-1 Tat interactions are homologous with acetyltransferases. Nat Genet 14: 42–49.

    CAS  PubMed  Google Scholar 

  • Richon VM, Emiliani S, Verdin E, Webb Y, Breslow R, Rifkind RA et al. (1998). A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. Proc Natl Acad Sci USA 95: 3003–3007.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Riggs MG, Whittaker RG, Neumann JR, Ingram VM . (1977). n-Butyrate causes histone modification in HeLa and Friend erythroleukaemia cells. Nature 268: 462–464.

    CAS  PubMed  Google Scholar 

  • Ropero S, Fraga MF, Ballestar E, Hamelin R, Yamamoto H, Boix-Chornet M et al. (2006). A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition. Nat Genet 38: 566–569.

    CAS  PubMed  Google Scholar 

  • Roth SY, Denu JM, Allis CD . (2001). Histone acetyltransferases. Annu Rev Biochem 70: 81–120.

    CAS  PubMed  Google Scholar 

  • Rundlett SE, Carmen AA, Kobayashi R, Bavykin S, Turner BM, Grunstein M . (1996). HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that regulate silencing and transcription. Proc Natl Acad Sci USA 93: 14503–14508.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sakaguchi K, Herrera JE, Saito S, Miki T, Bustin M, Vassilev A et al. (1998). DNA damage activates p53 through a phosphorylation–acetylation cascade. Genes Dev 12: 2831–2841.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Saleh A, Schieltz D, Ting N, McMahon SB, Litchfield DW, Yates JR et al. (1998). Tra1p is a component of the yeast Ada.Spt transcriptional regulatory complexes. J Biol Chem 273: 26559–26565.

    CAS  PubMed  Google Scholar 

  • Saunders LR, Verdin E . (2007). Sirtuins: critical regulators at the crossroads between cancer and aging. Oncogene 26: 5489–5504.

    CAS  PubMed  Google Scholar 

  • Schwer B, Bunkenborg J, Verdin RO, Andersen JS, Verdin E . (2006). Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc Natl Acad Sci U S A 103: 10224–10229.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sealy L, Chalkley R . (1978). The effect of sodium butyrate on histone modification. Cell 14: 115–121.

    CAS  PubMed  Google Scholar 

  • Seet BT, Dikic I, Zhou MM, Pawson T . (2006). Reading protein modifications with interaction domains. Nat Rev Mol Cell Biol 7: 473–483.

    CAS  PubMed  Google Scholar 

  • Shahbazian MD, Grunstein M . (2007). Functions of site-specific histone acetylation and deacetylation. Annu Rev Biochem 76: 26.1–26.26.

    Google Scholar 

  • Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, et al. (2004). Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119: 941–953.

    CAS  PubMed  Google Scholar 

  • Starai VJ, Celic I, Cole RN, Boeke JD, Escalante-Semerena JC . (2002). Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine. Science 298: 2390–2392.

    CAS  PubMed  Google Scholar 

  • Sterner DE, Berger SL . (2000). Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev 64: 435–459.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sterner R, Vidali G, Allfrey VG . (1979). Studies of acetylation and deacetylation in high mobility group proteins. Identification of the sites of acetylation in HMG-1. J Biol Chem 254: 11577–11583.

    CAS  PubMed  Google Scholar 

  • Straub T, Becker PB . (2007). Dosage compensation: the beginning and end of generalization. Nat Rev Genet 8: 47–57.

    CAS  PubMed  Google Scholar 

  • Sykes SM, Mellert HS, Holbert MA, Li K, Marmorstein R, Lane WS et al. (2006). Acetylation of the p53 DNA-binding domain regulates apoptosis induction. Mol Cell 24: 841–851.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tahiliani M, Mei P, Fang R, Leonor T, Rutenberg M, Shimizu F et al. (2007). The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation. Nature 447: 601–605.

    CAS  PubMed  Google Scholar 

  • Tang Y, Luo J, Zhang W, Gu W . (2006). Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis. Mol Cell 24: 827–839.

    CAS  PubMed  Google Scholar 

  • Taunton J, Hassig CA, Schreiber SL . (1996). A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 272: 408–411.

    CAS  PubMed  Google Scholar 

  • Toleman C, Paterson AJ, Whisenhunt TR, Kudlow JE . (2004). Characterization of the histone acetyltransferase (HAT) domain of a bifunctional protein with activable O-GlcNAcase and HAT activities. J Biol Chem 279: 53665–53673.

    CAS  PubMed  Google Scholar 

  • Trivedi CM, Luo Y, Yin Z, Zhang M, Zhu W, Wang T et al. (2007). Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3beta activity. Nat Med 13: 324–331.

    CAS  PubMed  Google Scholar 

  • Tsubota T, Berndsen CE, Erkmann JA, Smith CL, Yang L, Freitas MA et al. (2007). Histone H3-K56 acetylation is catalyzed by histone chaperone-dependent complexes. Mol Cell 25: 703–712.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Turner BM . (1993). Decoding the nucleosome. Cell 75: 5–8.

    CAS  PubMed  Google Scholar 

  • van der Linden AM, Nolan KM, Sengupta P . (2007). KIN-29 SIK regulates chemoreceptor gene expression via an MEF2 transcription factor and a class II HDAC. EMBO J 26: 358–370.

    CAS  PubMed  Google Scholar 

  • Vaquero A, Sternglanz R, Reinberg D . (2007). NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs. Oncogene 26: 5505–5520.

    CAS  PubMed  Google Scholar 

  • Vassilev A, Yamauchi J, Kotani T, Prives C, Avantaggiati ML, Qin J et al. (1998). The 400 kDa subunit of the PCAF histone acetylase complex belongs to the ATM superfamily. Mol Cell 2: 869–875.

    CAS  PubMed  Google Scholar 

  • Wolffe AP . (1994). Transcription: in tune with the histones. Cell 77: 13–16.

    CAS  PubMed  Google Scholar 

  • Xhemalce B, Miller KM, Driscoll R, Masumoto H, Jackson SP, Kouzarides T et al. (2007). Regulation of histone H3 lysine 56 acetylation in Schizosaccharomyces pombe. J Biol Chem 282: 15040–15047.

    CAS  PubMed  Google Scholar 

  • Xie H, Bandhakavi S, Roe MR, Griffin TJ . (2007). Preparative peptide isoelectric focusing as a tool for improving the identification of lysine-acetylated peptides from complex mixtures. J Proteome Res 6: 2019–2026.

    CAS  PubMed  Google Scholar 

  • Xu WS, Parmigiani RB, Marks PA . (2007). Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene 26: 5541–5552.

    CAS  PubMed  Google Scholar 

  • Yamada T, Fischle W, Sugiyama T, Allis CD, Grewal SI . (2005). The nucleation and maintenance of heterochromatin by a histone deacetylase in fission yeast. Mol Cell 20: 173–185.

    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  PubMed Central  Google Scholar 

  • Yang WM, Inouye C, Zeng Y, Bearss D, Seto E . (1996a). Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3. Proc Natl Acad Sci USA 93: 12845–12850.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang XJ, Grégoire S . (2007). Metabolism, cytoskeleton and cellular signaling in the grip of protein Nɛ- and O-acetylation. EMBO Rep 8: 556–562.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang XJ, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y . (1996b). A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature 382: 319–324.

    CAS  PubMed  Google Scholar 

  • Yang X-J, Ullah M . (2007). MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells. Oncogene 26: 5408–5419.

    CAS  PubMed  Google Scholar 

  • Yoshida M, Kijima M, Akita M, Beppu T . (1990). Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem 265: 17174–17179.

    CAS  PubMed  Google Scholar 

  • Zaratiegui M, Irvine DV, Martienssen RA . (2007). Noncoding RNAs and gene silencing. Cell 128: 763–776.

    CAS  PubMed  Google Scholar 

  • Zhang X, Ozawa Y, Lee H, Wen YD, Tan TH, Wadzinski BE, et al. (2005). Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4. Genes Dev 19: 827–839.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, LeRoy G, Seelig HP, Lane WS, Reinberg D . (1998). The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Cell 95: 279–289.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful to Dr Prem Reddy for vision and support, the contributors for enthusiasm and ∼40 anonymous referees for critical evaluation of the articles. We apologize to those whose works are unintentionally omitted in this issue because of knowledge and space limitation. Our research has been supported by grants from the NIH (to ES) and the Canadian funding agencies NCIC, CIHR, CFI and NSERC (to XJY).

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Authors and Affiliations

  1. Department of Medicine, Molecular Oncology Group, McGill University Health Center, Montréal, Québec, Canada

    X-J Yang

  2. Molecular Oncology Program, H Lee Moffitt Cancer Center, Tampa, FL, USA

    E Seto

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  1. X-J Yang
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  2. E Seto
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Correspondence to X-J Yang or E Seto.

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Yang, XJ., Seto, E. HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene 26, 5310–5318 (2007). https://doi.org/10.1038/sj.onc.1210599

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