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| The EMBO Journal
(2000) 19, 662–671, doi:10.1093/emboj/19.4.662 |
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| Regulation of E2F1 activity by acetylation |
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| Marian A. Martínez-Balbás1, 2, Uta-Maria Bauer1, 2, Søren J. Nielsen1, Alexander Brehm1 and Tony Kouzarides1 |
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1 Wellcome/CRC Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK 2 M.A.Martínez-Balbás and U.-M.Bauer contributed equally to this work To whom correspondence should be addressed Tony Kouzarides, tk106@mole.bio.cam.ac.uk Received 9 September 1999; Revised 9 December 1999; Accepted 9 December 1999. |
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| Abstract |
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| During the G1 phase of the cell cycle, an E2F–RB complex represses transcription, via the recruitment of histone deacetylase activity. Phosphorylation of RB at the G1/S boundary generates a pool of 'free' E2F, which then stimulates transcription of S-phase genes. Given that E2F1 activity is stimulated by p300/CBP acetylase and repressed by an RB-associated deacetylase, we asked if E2F1 was subject to modification by acetylation. We show that the p300/CBP-associated factor P/CAF, and to a lesser extent p300/CBP itself, can acetylate E2F1 in vitro and that intracellular E2F1 is acetylated. The acetylation sites lie adjacent to the E2F1 DNA-binding domain and involve lysine residues highly conserved in E2F1, 2 and 3. Acetylation by P/CAF has three functional consequences on E2F1 activity: increased DNA-binding ability, activation potential and protein half-life. These results suggest that acetylation stimulates the functions of the non-RB bound 'free' form of E2F1. Consistent with this, we find that the RB-associated histone deacetylase can deacetylate E2F1. These results identify acetylation as a novel regulatory modification that stimulates E2F1's activation functions. |
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| Keywords: acetylation, E2F1, histone deacetylase, p300, P, CAF, retinoblastoma protein |
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