E2F family members are differentially regulated by reversible acetylation

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 ge nes involved in DNA replication and cell proliferation. E2F-1, -2, and -3 b elong to a structural and functional subfamily distinct from those of the o ther 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 co nserved lysine residues located at the N-terminal boundary of their DNA bin ding domains. Acetylation of E2F-1 in vitro and in vivo markedly increases its binding affinity for a consensus E2F DNA-binding site, which is paralle led by enhanced transactivation of an E2F-responsive promoter. Acetylation of E2F-1 can be reversed by histone deacetylase-1, indicating that reversib le acetylation is a mechanism for regulation also of non-histone proteins.