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| The EMBO Journal
(2001) 20, 1984–1992, doi:10.1093/emboj/20.8.1984 |
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| Transcription factor-dependent regulation of CBP and P/CAF histone acetyltransferase activity |
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| Evi Soutoglou1, 4, Benoit Viollet2, 4, Martine Vaxillaire2, 3, Moshe Yaniv2, Marco Pontoglio2 and Iannis Talianidis1 |
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1 Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, PO Box 1527, 711 10 Heraklion, Crete, Greece 2 Unite des Virus Oncogenes, CNRS, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris, Cedex 15, France 3 Present address: CNRS EP-10, Institut Pasteur de Lille, Lille, France 4 E.Soutoglou and B.Viollet contributed equally to this work To whom correspondence should be addressed Iannis Talianidis, talianid@imbb.forth.gr Received 2 January 2001; Revised 12 February 2001; Accepted 20 February 2001. |
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| Abstract |
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CREB-binding protein (CBP) and CBP-associated factor (P/CAF) are coactivators possessing an intrinsic histone acetyltransferase (HAT) activity. They are positioned at promoter regions via association with sequence-specific DNA-binding factors and stimulate transcription in a gene-specific manner. The current view suggests that coactivator function depends mainly on the strength and specificity of transcription factor–coactivator interactions. Here we show that two dominant-negative mutants of hepatocyte nuclear factor-1 (HNF-1), P447L and P519L, occurring in maturity onset diabetes of the young (MODY3) patients, exhibit paradoxically stronger interactions than the wild-type protein with either CBP or P/CAF. However, CBP and P/CAF recruited by these mutants lack HAT activity. In contrast, wild-type HNF-1 and other transcription factors, such as Sp1 or HNF-4, stimulated the HAT activity of CBP. The results suggest a more dynamic role for DNA-binding proteins in the transcription process than was considered previously. They are not only required for the recruitment of coactivators to the promoter but they may also modulate their enzymatic activity. |
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| Keywords: acetylation, chromatin, diabetes, hepatocyte, transcription |
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