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The MYST family of histone acetyltransferases and their intimate links to cancer

Abstract

The histone acetyltransferases (HATs) of the MYST family are highly conserved in eukaryotes and carry out a significant proportion of all nuclear acetylation. These enzymes function exclusively in multisubunit protein complexes whose composition is also evolutionarily conserved. MYST HATs are involved in a number of key nuclear processes and play critical roles in gene-specific transcription regulation, DNA damage response and repair, as well as DNA replication. This suggests that anomalous activity of these HATs or their associated complexes can easily lead to severe cellular malfunction, resulting in cell death or uncontrolled growth and malignancy. Indeed, the MYST family HATs have been implicated in several forms of human cancer. This review summarizes the current understanding of these enzymes and their normal function, as well as their established and putative links to oncogenesis.

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References

  • Aggarwal BD, Calvi BR . (2004). Chromatin regulates origin activity in Drosophila follicle cells. Nature 430: 372–376.

    CAS  PubMed  Google Scholar 

  • Awasthi S, Sharma A, Wong K, Zhang J, Matlock EF, Rogers L et al. (2005). A human T-cell lymphotropic virus type 1 enhancer of Myc transforming potential stabilizes Myc-TIP60 transcriptional interactions. Mol Cell Biol 25: 6178–6198.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Baek SH, Ohgi KA, Rose DW, Koo EH, Glass CK, Rosenfeld MG . (2002). Exchange of N-CoR corepressor and Tip60 co-activator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein. Cell 110: 55–67.

    CAS  PubMed  Google Scholar 

  • Berns K, Hijmans EM, Mullenders J, Brummelkamp TR, Velds A, Heimerikx M et al. (2004). A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature 428: 431–437.

    CAS  PubMed  Google Scholar 

  • Bertram MJ, Berube NG, Hang-Swanson X, Ran Q, Leung JK, Bryce S et al. (1999). Identification of a gene that reverses the immortal phenotype of a subset of cells and is a member of a novel family of transcription factor-like genes. Mol Cell Biol 19: 1479–1485.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bertram MJ, Pereira-Smith OM . (2001). Conservation of the MORF4 related gene family: identification of a new chromo domain subfamily and novel protein motif. Gene 266: 111–121.

    CAS  PubMed  Google Scholar 

  • Bewersdorf J, Bennett BT, Knight KL . (2006). H2AX chromatin structures and their response to DNA damage revealed by 4Pi microscopy. Proc Natl Acad Sci USA 103: 18137–18142.

    CAS  PubMed  PubMed Central  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 

  • Boudreault AA, Cronier D, Selleck W, Lacoste N, Utley RT, Allard S et al. (2003). Yeast enhancer of polycomb defines global Esa1-dependent acetylation of chromatin. Genes Dev 17: 1415–1428.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Burke TW, Cook JG, Asano M, Nevins JR . (2001). Replication factors MCM2 and ORC1 interact with the histone acetyltransferase HBO1. J Biol Chem 276: 15397–15408.

    CAS  PubMed  Google Scholar 

  • Camos M, Esteve J, Jares P, Colomer D, Rozman M, Villamor N et al. (2006). Gene expression profiling of acute myeloid leukemia with translocation t(8;16)(p11;p13) and MYST3-CREBBP rearrangement reveals a distinctive signature with a specific pattern of HOX gene expression. Cancer Res 66: 6947–6954.

    CAS  PubMed  Google Scholar 

  • Campos EI, Chin MY, Kuo WH, Li G . (2004). Biological functions of the ING family tumor suppressors. Cell Mol Life Sci 61: 2597–2613.

    CAS  PubMed  Google Scholar 

  • Cao X, Sudhof TC . (2001). A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltransferase Tip60. Science 293: 115–120.

    CAS  PubMed  Google Scholar 

  • Cao X, Sudhof TC . (2004). Dissection of amyloid-beta precursor protein-dependent transcriptional transactivation. J Biol Chem 279: 24601–24611.

    CAS  PubMed  Google Scholar 

  • Carapeti M, Aguiar RC, Goldman JM, Cross NC . (1998). A novel fusion between MOZ and the nuclear receptor co-activator TIF2 in acute myeloid leukemia. Blood 91: 3127–3133.

    CAS  PubMed  Google Scholar 

  • Chamberlin HM, Thomas JH . (2000). The bromodomain protein LIN-49 and trithorax-related protein LIN-59 affect development and gene expression in Caenorhabditis elegans. Development 127: 713–723.

    CAS  PubMed  Google Scholar 

  • Champagne N, Bertos NR, Pelletier N, Wang AH, Vezmar M, Yang Y et al. (1999). Identification of a human histone acetyltransferase related to monocytic leukemia zinc finger protein. J Biol Chem 274: 28528–28536.

    CAS  PubMed  Google Scholar 

  • Champagne N, Pelletier N, Yang XJ . (2001). The monocytic leukemia zinc finger protein MOZ is a histone acetyltransferase. Oncogene 20: 404–409.

    CAS  PubMed  Google Scholar 

  • Chan HM, Narita M, Lowe SW, Livingston DM . (2005). The p400 E1A-associated protein is a novel component of the p53 → p21 senescence pathway. Genes Dev 19: 196–201.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chang S, Johnston Jr RJ, Hobert O . (2003). A transcriptional regulatory cascade that controls left/right asymmetry in chemosensory neurons of C. elegans. Genes Dev 17: 2123–2137.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chaudhuri B, Xu H, Todorov I, Dutta A, Yates JL . (2001). Human DNA replication initiation factors, ORC and MCM, associate with oriP of Epstein–Barr virus. Proc Natl Acad Sci USA 98: 10085–10089.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chowdhury D, Keogh MC, Ishii H, Peterson CL, Buratowski S, Lieberman J . (2005). Gamma-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair. Mol Cell 20: 801–809.

    CAS  PubMed  Google Scholar 

  • Col E, Caron C, Chable-Bessia C, Legube G, Gazzeri S, Komatsu Y et al. (2005). HIV-1 Tat targets Tip60 to impair the apoptotic cell response to genotoxic stresses. EMBO J 24: 2634–2645.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Collins HM, Kindle KB, Matsuda S, Ryan C, Troke PJ, Kalkhoven E et al. (2006). MOZ-TIF2 alters cofactor recruitment and histone modification at the RARbeta 2 promoter: differential effects of MOZ fusion proteins on CBP-and MOZ-dependent activators. J Biol Chem 281: 17124–17133.

    CAS  PubMed  Google Scholar 

  • Contzler R, Regamey A, Favre B, Roger T, Hohl D, Huber M . (2006). Histone acetyltransferase HBO1 inhibits NF-kappaB activity by co-activator sequestration. Biochem Biophys Res Commun 350: 208–213.

    CAS  PubMed  Google Scholar 

  • Creaven M, Hans F, Mutskov V, Col E, Caron C, Dimitrov S et al. (1999). Control of the histone-acetyltransferase activity of Tip60 by the HIV-1 transactivator protein, Tat. Biochemistry 38: 8826–8830.

    CAS  PubMed  Google Scholar 

  • DePamphilis ML . (2003). The ‘ORC cycle’: a novel pathway for regulating eukaryotic DNA replication. Gene 310: 1–15.

    CAS  PubMed  Google Scholar 

  • Dhar SK, Yoshida K, Machida Y, Khaira P, Chaudhuri B, Wohlschlegel JA et al. (2001). Replication from oriP of Epstein–Barr virus requires human ORC and is inhibited by geminin. Cell 106: 287–296.

    CAS  PubMed  Google Scholar 

  • Downs JA, Allard S, Jobin-Robitaille O, Javaheri A, Auger A, Bouchard N et al. (2004). Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites. Mol Cell 16: 979–990.

    CAS  PubMed  Google Scholar 

  • Doyon Y, Cayrou C, Ullah M, Landry AJ, Cote V, Selleck W et al. (2006). ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell 21: 51–64.

    CAS  PubMed  Google Scholar 

  • Doyon Y, Selleck W, Lane WS, Tan S, Cote J . (2004). Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol 24: 1884–1896.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dugan KA, Wood MA, Cole MD . (2002). TIP49, but not TRRAP, modulates c-Myc and E2F1 dependent apoptosis. Oncogene 21: 5835–5843.

    CAS  PubMed  Google Scholar 

  • Eymin B, Claverie P, Salon C, Leduc C, Col E, Brambilla E et al. (2006). p14ARF activates a Tip60-dependent and p53-independent ATM/ATR/CHK pathway in response to genotoxic stress. Mol Cell Biol 26: 4339–4350.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fischer U, Heckel D, Michel A, Janka M, Hulsebos T, Meese E . (1997). Cloning of a novel transcription factor-like gene amplified in human glioma including astrocytoma grade I. Hum Mol Genet 6: 1817–1822.

    CAS  PubMed  Google Scholar 

  • Frank SR, Parisi T, Taubert S, Fernandez P, Fuchs M, Chan HM et al. (2003). MYC recruits the TIP60 histone acetyltransferase complex to chromatin. EMBO Rep 4: 575–580.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fuchs M, Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V et al. (2001). The p400 complex is an essential E1A transformation target. Cell 106: 297–307.

    CAS  PubMed  Google Scholar 

  • Garkavtsev I, Grigorian IA, Ossovskaya VS, Chernov MV, Chumakov PM, Gudkov AV . (1998). The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control. Nature 391: 295–298.

    CAS  PubMed  Google Scholar 

  • Garkavtsev I, Kazarov A, Gudkov A, Riabowol K . (1996). Suppression of the novel growth inhibitor p33ING1 promotes neoplastic transformation. Nat Genet 14: 415–420.

    CAS  PubMed  Google Scholar 

  • Garkavtsev I, Kozin SV, Chernova O, Xu L, Winkler F, Brown E et al. (2004). The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis. Nature 428: 328–332.

    Article  CAS  PubMed  Google Scholar 

  • Gaughan L, Brady ME, Cook S, Neal DE, Robson CN . (2001). Tip60 is a co-activator specific for class I nuclear hormone receptors. J Biol Chem 276: 46841–46848.

    CAS  PubMed  Google Scholar 

  • Gaughan L, Logan IR, Cook S, Neal DE, Robson CN . (2002). Tip60 and histone deacetylase 1 regulate androgen receptor activity through changes to the acetylation status of the receptor. J Biol Chem 277: 25904–25913.

    CAS  PubMed  Google Scholar 

  • Georgiakaki M, Chabbert-Buffet N, Dasen B, Meduri G, Wenk S, Rajhi L et al. (2006). Ligand-controlled interaction of HBO1 with the N-terminal transactivating domain of progesterone receptor induces SRC-1-dependent co-activation of transcription. Mol Endocrinol 20: 2122–2140.

    CAS  PubMed  Google Scholar 

  • Grienenberger A, Miotto B, Sagnier T, Cavalli G, Schramke V, Geli V et al. (2002). The MYST domain acetyltransferase Chameau functions in epigenetic mechanisms of transcriptional repression. Curr Biol 12: 762–766.

    CAS  PubMed  Google Scholar 

  • Gunduz M, Ouchida M, Fukushima K, Ito S, Jitsumori Y, Nakashima T et al. (2002). Allelic loss and reduced expression of the ING3, a candidate tumor suppressor gene at 7q31, in human head and neck cancers. Oncogene 21: 4462–4470.

    CAS  PubMed  Google Scholar 

  • Halkidou K, Gnanapragasam VJ, Mehta PB, Logan IR, Brady ME, Cook S et al. (2003). Expression of Tip60, an androgen receptor co-activator, and its role in prostate cancer development. Oncogene 22: 2466–2477.

    CAS  PubMed  Google Scholar 

  • He GH, Helbing CC, Wagner MJ, Sensen CW, Riabowol K . (2005). Phylogenetic analysis of the ING family of PHD finger proteins. Mol Biol Evol 22: 104–116.

    CAS  PubMed  Google Scholar 

  • Hicks DG, Yoder BJ, Short S, Tarr S, Prescott N, Crowe JP et al. (2006). Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients. Clin Cancer Res 12: 6702–6708.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hobbs CA, Wei G, Defeo K, Paul B, Hayes CS, Gilmour SK . (2006). Tip60 protein isoforms and altered function in skin and tumors that overexpress ornithine decarboxylase. Cancer Res 66: 8116–8122.

    CAS  PubMed  Google Scholar 

  • Horn PJ, Peterson CL . (2002). Molecular biology. Chromatin higher order folding – wrapping up transcription. Science 297: 1824–1827.

    CAS  PubMed  Google Scholar 

  • Huntly BJ, Shigematsu H, Deguchi K, Lee BH, Mizuno S, Duclos N et al. (2004). MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell 6: 587–596.

    CAS  PubMed  Google Scholar 

  • Iizuka M, Matsui T, Takisawa H, Smith MM . (2006). Regulation of replication licensing by acetyltransferase Hbo1. Mol Cell Biol 26: 1098–1108.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Iizuka M, Stillman B . (1999). Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein. J Biol Chem 274: 23027–23034.

    CAS  PubMed  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 

  • 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 

  • Katsumoto T, Aikawa Y, Iwama A, Ueda S, Ichikawa H, Ochiya T et al. (2006). MOZ is essential for maintenance of hematopoietic stem cells. Genes Dev 20: 1321–1330.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Keogh MC, Kim JA, Downey M, Fillingham J, Chowdhury D, Harrison JC et al. (2006). A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature 439: 497–501.

    CAS  PubMed  Google Scholar 

  • Kim JH, Kim B, Cai L, Choi HJ, Ohgi KA, Tran C et al. (2005). Transcriptional regulation of a metastasis suppressor gene by Tip60 and beta-catenin complexes. Nature 434: 921–926.

    CAS  PubMed  Google Scholar 

  • Kim S, Chin K, Gray JW, Bishop JM . (2004). A screen for genes that suppress loss of contact inhibition: identification of ING4 as a candidate tumor suppressor gene in human cancer. Proc Natl Acad Sci USA 101: 16251–16256.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kinoshita A, Whelan CM, Berezovska O, Hyman BT . (2002). The gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein induces apoptosis via Tip60 in H4 cells. J Biol Chem 277: 28530–28536.

    CAS  PubMed  Google Scholar 

  • Kitabayashi I, Aikawa Y, Nguyen LA, Yokoyama A, Ohki M . (2001a). Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein. EMBO J 20: 7184–7196.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kitabayashi I, Aikawa Y, Yokoyama A, Hosoda F, Nagai M, Kakazu N et al. (2001b). Fusion of MOZ and p300 histone acetyltransferases in acute monocytic leukemia with a t(8;22)(p11;q13) chromosome translocation. Leukemia 15: 89–94.

    CAS  PubMed  Google Scholar 

  • Knoops L, Renauld JC . (2004). IL-9 and its receptor: from signal transduction to tumorigenesis. Growth Factors 22: 207–215.

    CAS  PubMed  Google Scholar 

  • Kojima K, Kaneda K, Yoshida C, Dansako H, Fujii N, Yano T et al. (2003). A novel fusion variant of the MORF and CBP genes detected in therapy-related myelodysplastic syndrome with t(10;16)(q22;p13). Br J Haematol 120: 271–273.

    CAS  PubMed  Google Scholar 

  • Kusch T, Florens L, Macdonald WH, Swanson SK, Glaser RL, Yates III JR et al. (2004). Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions. Science 306: 2084–2087.

    CAS  PubMed  Google Scholar 

  • Kuzmichev A, Zhang Y, Erdjument-Bromage H, Tempst P, Reinberg D . (2002). Role of the Sin3-histone deacetylase complex in growth regulation by the candidate tumor suppressor p33(ING1). Mol Cell Biol 22: 835–848.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lafon N, Chang CS, Scott EM, Jacobson SJ, Pillus L . (2007). Oncogene (in press).

  • Lai A, Kennedy BK, Barbie DA, Bertos NR, Yang XJ, Theberge MC et al. (2001). RBP1 recruits the mSIN3-histone deacetylase complex to the pocket of retinoblastoma tumor suppressor family proteins found in limited discrete regions of the nucleus at growth arrest. Mol Cell Biol 21: 2918–2932.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lang SE, Hearing P . (2003). The adenovirus E1A oncoprotein recruits the cellular TRRAP/GCN5 histone acetyltransferase complex. Oncogene 22: 2836–2841.

    CAS  PubMed  Google Scholar 

  • Leduc C, Claverie P, Eymin B, Col E, Khochbin S, Brambilla E et al. (2006). p14(ARF) promotes RB accumulation through inhibition of its Tip60-dependent acetylation. Oncogene 25: 4147–4154.

    CAS  PubMed  Google Scholar 

  • Legube G, Linares LK, Tyteca S, Caron C, Scheffner M, Chevillard-Briet M et al. (2004). Role of the histone acetyl transferase Tip60 in the p53 pathway. J Biol Chem 279: 44825–44833.

    CAS  PubMed  Google Scholar 

  • Linggi BE, Brandt SJ, Sun ZW, Hiebert SW . (2005). Translating the histone code into leukemia. J Cell Biochem 96: 938–950.

    CAS  PubMed  Google Scholar 

  • Liu Y, Smith PW, Jones DR . (2006). Breast cancer metastasis suppressor 1 functions as a corepressor by enhancing histone deacetylase 1-mediated deacetylation of RelA/p65 and promoting apoptosis. Mol Cell Biol 26: 8683–8696.

    CAS  PubMed  PubMed Central  Google Scholar 

  • LLeonart ME, Vidal F, Gallardo D, Diaz-Fuertes M, Rojo F, Cuatrecasas M et al. (2006). New p53 related genes in human tumors: significant downregulation in colon and lung carcinomas. Oncol Rep 16: 603–608.

    CAS  PubMed  Google Scholar 

  • Lund AH, Turner G, Trubetskoy A, Verhoeven E, Wientjens E, Hulsman D et al. (2002). Genome-wide retroviral insertional tagging of genes involved in cancer in Cdkn2a-deficient mice. Nat Genet 32: 160–165.

    CAS  PubMed  Google Scholar 

  • Meehan WJ, Samant RS, Hopper JE, Carrozza MJ, Shevde LA, Workman JL et al. (2004). Breast cancer metastasis suppressor 1 (BRMS1) forms complexes with retinoblastoma-binding protein 1 (RBP1) and the mSin3 histone deacetylase complex and represses transcription. J Biol Chem 279: 1562–1569.

    CAS  PubMed  Google Scholar 

  • Meehan WJ, Welch DR . (2003). Breast cancer metastasis suppressor 1: update. Clin Exp Metastasis 20: 45–50.

    CAS  PubMed  Google Scholar 

  • Merson TD, Dixon MP, Collin C, Rietze RL, Bartlett PF, Thomas T et al. (2006). The transcriptional co-activator Querkopf controls adult neurogenesis. J Neurosci 26: 11359–11370.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Micci F, Panagopoulos I, Bjerkehagen B, Heim S . (2006). Consistent rearrangement of chromosomal band 6p21 with generation of fusion genes JAZF1/PHF1 and EPC1/PHF1 in endometrial stromal sarcoma. Cancer Res 66: 107–112.

    CAS  PubMed  Google Scholar 

  • Miotto B, Sagnier T, Berenger H, Bohmann D, Pradel J, Graba Y . (2006). Chameau HAT and DRpd3 HDAC function as antagonistic cofactors of JNK/AP-1-dependent transcription during Drosophila metamorphosis. Genes Dev 20: 101–112.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Monden T, Wondisford FE, Hollenberg AN . (1997). Isolation and characterization of a novel ligand-dependent thyroid hormone receptor-co-activating protein. J Biol Chem 272: 29834–29841.

    CAS  PubMed  Google Scholar 

  • Moore SD, Herrick SR, Ince TA, Kleinman MS, Cin PD, Morton CC et al. (2004). Uterine leiomyomata with t(10;17) disrupt the histone acetyltransferase MORF. Cancer Res 64: 5570–5577.

    CAS  PubMed  Google Scholar 

  • Murr R, Loizou JI, Yang YG, Cuenin C, Li H, Wang ZQ et al. (2006). Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks. Nat Cell Biol 8: 91–99.

    CAS  PubMed  Google Scholar 

  • Nagashima M, Shiseki M, Miura K, Hagiwara K, Linke SP, Pedeux R et al. (2001). DNA damage-inducible gene p33ING2 negatively regulates cell proliferation through acetylation of p53. Proc Natl Acad Sci USA 98: 9671–9676.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nagashima M, Shiseki M, Pedeux RM, Okamura S, Kitahama-Shiseki M, Miura K et al. (2003). A novel PHD-finger motif protein, p47ING3, modulates p53-mediated transcription, cell cycle control, and apoptosis. Oncogene 22: 343–350.

    CAS  PubMed  Google Scholar 

  • Nesbit CE, Tersak JM, Prochownik EV . (1999). MYC oncogenes and human neoplastic disease. Oncogene 18: 3004–3016.

    CAS  PubMed  Google Scholar 

  • Nikiforov MA, Chandriani S, Park J, Kotenko I, Matheos D, Johnsson A et al. (2002). TRRAP-dependent and TRRAP-independent transcriptional activation by Myc family oncoproteins. Mol Cell Biol 22: 5054–5063.

    CAS  PubMed  PubMed Central  Google Scholar 

  • O’Connell S, Wang L, Robert S, Jones CA, Saint R, Jones RS . (2001). Polycomblike PHD fingers mediate conserved interaction with enhancer of zeste protein. J Biol Chem 276: 43065–43073.

    PubMed  Google Scholar 

  • Ohta K, Ohigashi M, Naganawa A, Ikeda H, Sakai M, Nishikawa JI et al. (2006). Histone acetyltransferase MOZ acts as a co-activator of Nrf2/MafK and induces tumor marker gene expression during hepatocarcinogenesis. Biochem J 3: 3.

    Google Scholar 

  • Panagopoulos I, Fioretos T, Isaksson M, Mitelman F, Johansson B, Theorin N et al. (2002). RT-PCR analysis of acute myeloid leukemia with t(8;16)(p11;p13): identification of a novel MOZ/CBP transcript and absence of CBP/MOZ expression. Genes Chromosomes Cancer 35: 372–374.

    CAS  PubMed  Google Scholar 

  • Panagopoulos I, Fioretos T, Isaksson M, Samuelsson U, Billstrom R, Strombeck B et al. (2001). Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10;16)(q22;p13). Hum Mol Genet 10: 395–404.

    CAS  PubMed  Google Scholar 

  • Park J, Wood MA, Cole MD . (2002). BAF53 forms distinct nuclear complexes and functions as a critical c-Myc-interacting nuclear cofactor for oncogenic transformation. Mol Cell Biol 22: 1307–1316.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Park JH, Roeder RG . (2006). GAS41 is required for repression of the p53 tumor suppressor pathway during normal cellular proliferation. Mol Cell Biol 26: 4006–4016.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pedeux R, Sengupta S, Shen JC, Demidov ON, Saito S, Onogi H et al. (2005). ING2 regulates the onset of replicative senescence by induction of p300-dependent p53 acetylation. Mol Cell Biol 25: 6639–6648.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pelletier N, Champagne N, Stifani S, Yang XJ . (2002). MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2. Oncogene 21: 2729–2740.

    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 

  • Radhakrishnan SK, Kamalakaran S . (2006). Pro-apoptotic role of NF-kappaB: Implications for cancer therapy. Biochim Biophys Acta 1766: 53–62.

    CAS  PubMed  Google Scholar 

  • Raho G, Miranda C, Tamborini E, Pierotti MA, Greco A . (2007). Detection of novel mRNA splice variants of human ING4 tumor suppressor gene. Oncogene 26: 26.

    Google Scholar 

  • Rea S, Xouri G, Akhtar A . (2007). Males absent on the first (MOF): from flies to humans. Oncogene 26: 5385–5395.

    CAS  PubMed  Google Scholar 

  • Renauld JC . (2001). New insights into the role of cytokines in asthma. J Clin Pathol 54: 577–589.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rogakou EP, Boon C, Redon C, Bonner WM . (1999). Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol 146: 905–916.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rozman M, Camos M, Colomer D, Villamor N, Esteve J, Costa D et al. (2004). Type I MOZ/CBP (MYST3/CREBBP) is the most common chimeric transcript in acute myeloid leukemia with t(8;16)(p11;p13) translocation. Genes Chromosomes Cancer 40: 140–145.

    CAS  PubMed  Google Scholar 

  • Russell M, Berardi P, Gong W, Riabowol K . (2006). Grow-ING, Age-ING and Die-ING: ING proteins link cancer, senescence and apoptosis. Exp Cell Res 312: 951–961.

    CAS  PubMed  Google Scholar 

  • Samant RS, Clark DW, Fillmore RA, Cicek M, Metge BJ, Chandramouli KH et al. (2007). Breast cancer metastasis suppressor 1 (BRMS1) inhibits osteopontin transcription by abrogating NF-kappaB activation. Mol Cancer 6: 6.

    PubMed  PubMed Central  Google Scholar 

  • Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S . (2004). Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 73: 39–85.

    CAS  PubMed  Google Scholar 

  • Scott M, Bonnefin P, Vieyra D, Boisvert FM, Young D, Bazett-Jones DP et al. (2001). UV-induced binding of ING1 to PCNA regulates the induction of apoptosis. J Cell Sci 114: 3455–3462.

    CAS  PubMed  Google Scholar 

  • Selleck W, Fortin I, Sermwittayawong D, Cote J, Tan S . (2005). The Saccharomyces cerevisiae Piccolo NuA4 histone acetyltransferase complex requires the Enhancer of Polycomb A domain and chromodomain to acetylate nucleosomes. Mol Cell Biol 25: 5535–5542.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Severinsen JE, Bjarkam CR, Kiaer-Larsen S, Olsen IM, Nielsen MM, Blechingberg J et al. (2006). Evidence implicating BRD1 with brain development and susceptibility to both schizophrenia and bipolar affective disorder. Mol Psychiatry 11: 1126–1138.

    CAS  PubMed  Google Scholar 

  • Sharma M, Zarnegar M, Li X, Lim B, Sun Z . (2000). Androgen receptor interacts with a novel MYST protein, HBO1. J Biol Chem 275: 35200–35208.

    CAS  PubMed  Google Scholar 

  • Shi X, Hong T, Walter KL, Ewalt M, Michishita E, Hung T et al. (2006). ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Nature 442: 96–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shiloh Y . (2003). ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer 3: 155–168.

    CAS  PubMed  Google Scholar 

  • Shimada Y, Saito A, Suzuki M, Takahashi E, Horie M . (1998). Cloning of a novel gene (ING1L) homologous to ING1, a candidate tumor suppressor. Cytogenet Cell Genet 83: 232–235.

    CAS  PubMed  Google Scholar 

  • Shimono Y, Murakami H, Hasegawa Y, Takahashi M . (2000). RET finger protein is a transcriptional repressor and interacts with enhancer of polycomb that has dual transcriptional functions. J Biol Chem 275: 39411–39419.

    CAS  PubMed  Google Scholar 

  • Shiseki M, Nagashima M, Pedeux RM, Kitahama-Shiseki M, Miura K, Okamura S et al. (2003). p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity. Cancer Res 63: 2373–2378.

    CAS  PubMed  Google Scholar 

  • Shroff R, Arbel-Eden A, Pilch D, Ira G, Bonner WM, Petrini JH et al. (2004). Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break. Curr Biol 14: 1703–1711.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sierra J, Yoshida T, Joazeiro CA, Jones KA . (2006). The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes. Genes Dev 20: 586–600.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Skowyra D, Zeremski M, Neznanov N, Li M, Choi Y, Uesugi M et al. (2001). Differential association of products of alternative transcripts of the candidate tumor suppressor ING1 with the mSin3/HDAC1 transcriptional corepressor complex. J Biol Chem 276: 8734–8739.

    CAS  PubMed  Google Scholar 

  • Sliva D, Zhu YX, Tsai S, Kamine J, Yang YC . (1999). Tip60 interacts with human interleukin-9 receptor alpha-chain. Biochem Biophys Res Commun 263: 149–155.

    CAS  PubMed  Google Scholar 

  • Smith ER, Cayrou C, Huang R, Lane WS, Cote J, Lucchesi JC . (2005). A human protein complex homologous to the Drosophila MSL complex is responsible for the majority of histone H4 acetylation at lysine 16. Mol Cell Biol 25: 9175–9188.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stedman W, Deng Z, Lu F, Lieberman PM . (2004). ORC, MCM, and histone hyperacetylation at the Kaposi's sarcoma-associated herpesvirus latent replication origin. J Virol 78: 12566–12575.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sun Y, Jiang X, Chen S, Fernandes N, Price BD . (2005). A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Proc Natl Acad Sci USA 102: 13182–13187.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Surapureddi S, Yu S, Bu H, Hashimoto T, Yeldandi AV, Kashireddy P et al. (2002). Identification of a transcriptionally active peroxisome proliferator-activated receptor alpha-interacting cofactor complex in rat liver and characterization of PRIC285 as a co-activator. Proc Natl Acad Sci USA 99: 11836–11841.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki T, Shen H, Akagi K, Morse HC, Malley JD, Naiman DQ et al. (2002). New genes involved in cancer identified by retroviral tagging. Nat Genet 32: 166–174.

    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 

  • 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 

  • Taubert S, Gorrini C, Frank SR, Parisi T, Fuchs M, Chan HM et al. (2004). E2F-dependent histone acetylation and recruitment of the Tip60 acetyltransferase complex to chromatin in late G1. Mol Cell Biol 24: 4546–4556.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Thomas T, Corcoran LM, Gugasyan R, Dixon MP, Brodnicki T, Nutt SL et al. (2006). Monocytic leukemia zinc finger protein is essential for the development of long-term reconstituting hematopoietic stem cells. Genes Dev 20: 1175–1186.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Thomas T, Voss AK, Chowdhury K, Gruss P . (2000). Querkopf, a MYST family histone acetyltransferase, is required for normal cerebral cortex development. Development 127: 2537–2548.

    CAS  PubMed  Google Scholar 

  • Tyteca S, Vandromme M, Legube G, Chevillard-Briet M, Trouche D . (2006). Tip60 and p400 are both required for UV-induced apoptosis but play antagonistic roles in cell cycle progression. EMBO J 25: 1680–1689.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Unoki M, Shen JC, Zheng ZM, Harris CC . (2006). Novel splice variants of ING4 and their possible roles in the regulation of cell growth and motility. J Biol Chem 281: 34677–34686.

    CAS  PubMed  Google Scholar 

  • Utley RT, Cote J . (2003). The MYST family of histone acetyltransferases. Curr Top Microbiol Immunol 274: 203–236.

    CAS  PubMed  Google Scholar 

  • Vaquero A, Loyola A, Reinberg D . (2003). The constantly changing face of chromatin. Sci Aging Knowledge Environ 2003: re4–20.

    PubMed  Google Scholar 

  • Wang Y, Li G . (2006). ING3 promotes UV-induced apoptosis via fas/caspase-8 pathway in melanoma cells. J Biol Chem 281: 11887–11893.

    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 

  • Zhang Z, Yamashita H, Toyama T, Yamamoto Y, Kawasoe T, Iwase H . (2006). Reduced expression of the breast cancer metastasis suppressor 1 mRNA is correlated with poor progress in breast cancer. Clin Cancer Res 12: 6410–6414.

    CAS  PubMed  Google Scholar 

  • Zhou MI, Foy RL, Chitalia VC, Zhao J, Panchenko MV, Wang H et al. (2005). Jade-1, a candidate renal tumor suppressor that promotes apoptosis. Proc Natl Acad Sci USA 102: 11035–11040.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Work in our laboratory is supported by operating grants from the Canadian Institutes of Health Research (CIHR). NA holds a CIHR/Institute of Aging Fellowship and JC is a CIHR Investigator.

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Avvakumov, N., Côté, J. The MYST family of histone acetyltransferases and their intimate links to cancer. Oncogene 26, 5395–5407 (2007). https://doi.org/10.1038/sj.onc.1210608

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