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 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.
Marzio
G
G
Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, 34012 Trieste, Italy.
Wagener
C
C
Gutierrez
M I
MI
Cartwright
P
P
Helin
K
K
Giacca
M
M
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000494:pharmacology; D056465:Retinoblastoma-Binding Protein 1; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D056465:Retinoblastoma-Binding Protein 1; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D004247:DNA; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases