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J. Biol. Chem. 275 (15): 10887-10892

© 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

J Biol Chem, Vol. 275, Issue 15, 10887-10892, April 14, 2000

E2F Family Members Are Differentially Regulated by Reversible Acetylation*

Giuseppe MarzioDagger §, Christian Wagener||, Maria Ines GutierrezDagger , Peter Cartwright||, Kristian Helin, and Mauro GiaccaDagger **

From the Dagger  Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, 34012 Trieste, Italy and  Department of Experimental Oncology, European Institute of Oncology, via Ripamonti 435, 20141 Milan, Italy

The six members of the E2F family of transcription factors play a key role in the control of cell cycle progression by regulating the expression of genes involved in DNA replication and cell proliferation. E2F-1, -2, and -3 belong to a structural and functional subfamily distinct from those of the other E2F family members. Here we report that E2F-1, -2, and -3, but not E2F-4, -5, and -6, associate with and are acetylated by p300 and cAMP-response element-binding protein acetyltransferases. Acetylation occurs at three conserved lysine residues located at the N-terminal boundary of their DNA binding domains. Acetylation of E2F-1 in vitro and in vivo markedly increases its binding affinity for a consensus E2F DNA-binding site, which is paralleled by enhanced transactivation of an E2F-responsive promoter. Acetylation of E2F-1 can be reversed by histone deacetylase-1, indicating that reversible acetylation is a mechanism for regulation also of non-histone proteins.

* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Current address: Dept. of Retrovirology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

|| Marie Curie fellows.

** To whom correspondence should be addressed: Molecular Medicine Laboratory, ICGEB, Padriciano 99, 34012 Trieste, Italy. Tel.: 39-40-3757.324; Fax: +39-40-226555; E-mail:

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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