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Deacetylase recruitment by the C/H3 domain of the acetyltransferase p300

Oncogene volume 23, pages 2177–2187 (2004)Cite this article

Abstract

The balance between acetylation and deacetylation of histone and nonhistone proteins controls gene expression in a variety of cellular processes, with transcription being activated by acetyltransferases and silenced by deacetylases. We report here the formation and enzymatic characterization of a complex between the acetyltransferase p300 and histone deacetylases. The C/H3 region of p300 was found to co-purify deacetylase activity from nuclear cell extracts. A prototype of class I histone deacetylases, HDAC1, interacts with p300 C/H3 domain in vitro and in vivo. The p300-binding protein E1A competes with HDAC1 for C/H3 binding; and, like E1A, HDAC1 overexpression interferes with either activation of Gal4p300 fusion protein or p300-dependent co-activation of two C/H3-binding proteins, MyoD and p53. The exposure to deacetylase inhibitors could reverse the dominant-negative effect of a C/H3 fragment insulated from the rest of the molecule, on MyoD- and p53-dependent transcription, whereas inhibition by E1A was resistant to trichostatin A. These data support the hypothesis that association between acetyltransferases and deacetylases can control the expression of genes implicated in cellular growth and differentiation, and suggest that the dominant-negative effect of the p300 C/H3 fragment relies on deacetylase recruitment.

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References

  • Arany Z, Newsome D, Oldread E, Livingston DM and Eckner R . (1995). Nature, 374, 81–84.

  • Archer SY and Hodin RA . (1999). Curr. Opin. Genet. Dev., 9, 171–174.

  • Avantaggiati ML, Ogryzko V, Gardner K, Giordano A, Levine AS and Kelly K . (1997). Cell, 89, 1175–1184.

  • Bannister AJ and Kouzarides T . (1996). Nature, 384, 641–643.

  • Bartl S, Taplick J, Lagger G, Khier H, Kuchler K and Seiser C . (1997). Mol. Cell. Biol., 17, 5033–5043.

  • Bird AP and Wolffe AP . (1999). Cell, 99, 451–454.

  • Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ and Kouzarides T . (1998). Nature, 391, 597–601.

  • Chakravarti D, Ogryzko V, Kao HY, Nash A, Chen H, Nakatani Y and Evans RM . (1999). Cell, 96, 393–403.

  • Chan HN and La Thangue NB . (2001). J. Cell Sci., 114, 2363–2373.

  • Cho H, Orphanides G, Sun X, Yang XJ, Ogryzko V, Lees E, Nakatani Y and Reinberg D . (1998). Mol. Cell. Biol., 18, 5355–5363.

  • Costanzo A, Merlo P, Pediconi N, Fulco M, Sartorelli V, Cole PA, Fontemaggi G, Fanciulli M, Schiltz L, Blandino G, Balsano C and Levrero M . (2002). Mol. Cell, 8, 1243–1254.

  • Cress WD and Seto E . (2000). J. Cell. Physiol., 184, 1–16.

  • Dallas PB, Yaciuk P and Moran E . (1997). J. Virol., 71, 1726–1731.

  • Eberharter A and Becker PB . (2002). EMBO Rep., 3, 224–229.

  • Eckner R, Yao TP, Oldread E and Livingston DM . (1996). Genes Dev., 10, 2478–2490.

  • Felzien LK, Farrell S, Betts JC, Mosavin R and Nabel GJ . (1999). Mol. Cell. Biol., 19, 4241–4246.

  • Giordano A and Avantaggiati ML . (1999). J. Cell. Physiol., 181, 218–230.

  • Girdwood D, Bumpass D, Vaughan OA, Thain A, Anderson LA, Snowden AW, Garcia-Wilson E, Perkins ND and Hay RT . (2003). Mol. Cell, 4, 1043–1054.

  • Goodman RH and Smolik S . (2000). Genes Dev., 14, 1553–1577.

  • Grozinger CM and Schreiber SL . (2002). Chem. Biol., 9, 3–16.

  • Gu W and Roeder RG . (1997). Cell, 90, 595–606.

  • Hamamori Y, Sartorelli V, Ogryzko V, Puri PL, Wu HY, Wang JY, Nakatani Y and Kedes L . (1999). Cell, 96, 405–413.

  • Howe L, Brown CE, Lechner T and Workman JL . (1999). Crit. Rev. Eukaryot. Gene Expression, 9, 231–243.

  • Iavarone A and Massague J . (1999). Mol. Cell. Biol., 1, 916–922.

  • Iezzi S, Cossu G, Nervi C, Sartorelli V and Puri PL . (2002). Proc. Natl. Acad. Sci. USA, 99, 7757–7762.

  • Janknecht R and Hunter T . (1996). Curr. Biol., 6, 951–954.

  • Johnston LA, Tapscott SJ and Eisen H . (1992). Mol. Cell. Biol., 11, 5123–5130.

  • Khochbin S, Verdel A, Lemercier C and Seigneurin-Berny D . (2001). Curr. Opin. Genet. Dev., 11, 162–166.

  • Kim TK, Kim TH and Maniatis T . (1998). Proc. Natl. Acad. Sci. USA, 95, 12191–12196.

  • Kouzarides T . (2000). EMBO J., 21, 2383–2396.

  • Kraus WL, Manning ET and Kadonaga JT . (1999). Mol. Cell. Biol., 19, 8123–8135.

  • Lundblad JR, Kwok RP, Laurance ME, Harter ML and Goodman RH . (1995). Nature, 374, 85–88.

  • Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L and Gu W . (2001). Cell, 107, 137–148.

  • Luo RX, Postigo AA and Dean DC . (1998). Cell, 92, 463–473.

  • Magnaghi-Jaulin L, Groisman R, Naguibneva I, Robin P, Lorain S, Le Villain JP, Troalen F, Trouche D and Harel-Bellan A . (1998). Nature, 391, 601–605.

  • Mal A, Sturniolo M, Schiltz RL, Ghosh MK and Harter ML . (2001). EMBO J., 20, 1739–1753.

  • Martinez-Balbas MA, Bauer UM, Nielsen SJ, Brehm A and Kouzarides T . (2000). EMBO J., 19, 662–671.

  • McKinsey TA, Zhang CL and Olson EN . (2001). Curr. Opin. Genet. Dev., 11, 497–504.

  • Nakajima T, Uchida C, Anderson SF, Lee CG, Hurwitz J, Parvin JD and Montminy M . (1997). Cell, 90, 1107–1112.

  • Newman BL, Lundblad JR, Chen Y and Smolik SM . (2002). Genetics, 162, 1675–1685.

  • O'Connor MJ, Zimmermann H, Nielsen S, Bernard HU and Kouzarides T . (1999). J. Virol., 73, 3574–3581.

  • Ogryzko VV, Kotani T, Zhang X, Schiltz RL, Howard T, Yang XJ, Howard BH, Qin J and Nakatani Y . (1998). Cell, 94, 35–44.

  • Ogryzko VV, Schiltz RL, Russanova V, Howard BH and Nakatani Y . (1996). Cell, 87, 953–959.

  • Polesskaya A, Duquet A, Naguibneva I, Weise C, Vervisch A, Bengal E, Hucho F, Robin P and Harel-Bellan A . (2000). J. Biol. Chem., 275, 34359–34364.

  • Puri PL, Sartorelli V, Yang XJ, Hamamori Y, Ogryzko VV, Howard BH, Kedes L, Wang JY, Graessmann A, Nakatani Y and Levrero M . (1997a). Mol. Cell, 1, 35–45.

  • Puri PL, Avantaggiati ML, Balsano C, Sang N, Graessmann A, Giordano A and Levrero M . (1997b). EMBO J., 16, 369–383.

  • Puri PL, Iezzi S, Stiegler P, Chen TT, Schiltz RL, Muscat GE, Giordano A, Kedes L, Wang JY and Sartorelli V . (2001). Mol. Cell, 8, 885–897.

  • Puri PL and Sartorelli V . (2000). J. Cell. Physiol., 185, 155–173.

  • Richon VM, Sandhoff TW, Rifkind RA and Marks PA . (2000). Proc. Natl. Acad. Sci. USA, 97, 10014–10019.

  • Sakaguchi K, Herrera JE, Saito S, Miki T, Bustin M, Vassilev A, Anderson CW and Appella E . (1998). Genes Dev., 18, 2831–2841.

  • Sang N, Avantaggiati ML and Giordano A . (1997). J. Cell. Biochem., 66, 277–285.

  • Sartorelli V and Puri PL . (2001). Front. Biosci., 6, D1024–D1047.

  • Sartorelli V, Huang J, Hamamori Y and Kedes L . (1997). Mol. Cell. Biol., 17, 1010–1026.

  • Sartorelli V, Puri PL, Hamamori Y, Ogryzko V, Chung G, Nakatani Y, Wang J Y and Kedes L . (1999). Mol. Cell, 4, 725–734.

  • Sterner DE and Berger SL . (2000). Microbiol. Mol. Biol. Rev., 64, 435–459.

  • Stiegler P, De Luca A, Bagella L and Giordano A . (1998). Cancer Res., 58, 5049–5052.

  • Strahl BD and Allis CD . (2000). Nature, 403, 41–45.

  • Taunton J, Hassig CA and Schreiber SL . (1996). Science, 272, 408–411.

  • Wade PA . (2001). Oncogene, 20, 3166–3173.

  • Whyte P, Williamson NM and Harlow E . (1989). Cell, 56, 67–75.

  • Yamagoe S, Kanno T, Kanno Y, Sasaki S, Siegel RM, Lenardo MJ, Humphrey G, Wang Y, Nakatani Y, Howard BH and Ozato K . (2003). Mol. Cell. Biol., 23, 1025–1033.

  • Yang XJ, Ogryzko VV, Nishikawa J, Howard BH and Nakatani Y . (1996). Cell, 87, 953–959.

  • Yuan W, Condorelli G, Caruso M, Felsani A and Giordano A . (1996). J. Biol. Chem., 271, 9009–9013.

  • Zeng L and Zhou MM . (2002). FEBS Lett., 513, 124–128.

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Acknowledgements

We thank Drs L Schreiber, A Harel-Bellan, KH Klempnauer, S Mink, N LaThangue and M Montminy for providing reagents. PLP is an Assistant Telethon Scientist, and CS and SVF are supported by (the Telethon Career grant to PLP. CS is also supported by) Sbarro Health Research Organization. PS and LB are supported by NIH grants to AG. ADL is recipient of Telethon Grant 273bi. CS dedicates this work to Letizia Lavermicocca for her encouragement and support.

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Author notes

  1. Cristiano Simone and Peter Stiegler: These authors contributed equally to this work

Authors and Affiliations

  1. Laboratory of Gene Expression, Dulbecco Telethon Institute (DTI) at Fondazione A Cesalpino, University of Roma La Sapienza, Italy

    Cristiano Simone, Sonia-Vanina Forcales & Pier Lorenzo Puri

  2. The Salk Institute for Biological Studies, Peptide Biology Laboratory, La Jolla, 92093, CA, USA

    Cristiano Simone & Pier Lorenzo Puri

  3. Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, 19122, PA, USA

    Cristiano Simone, Peter Stiegler, Luigi Bagella, Antonio De Luca & Antonio Giordano

  4. IRCCS Neuromed, Via Atinense 18, Pozzilli, 86077 (IS), Italy

    Antonio De Luca

  5. Laboratory of Muscle Biology, Muscle Gene Expression Group, NIAMS National Institutes of Health, Bethesda, 20892-2753, MD, USA

    Vittorio Sartorelli

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  1. Cristiano Simone
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Correspondence to Pier Lorenzo Puri.

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Simone, C., Stiegler, P., Forcales, SV. et al. Deacetylase recruitment by the C/H3 domain of the acetyltransferase p300. Oncogene 23, 2177–2187 (2004). https://doi.org/10.1038/sj.onc.1207327

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