C/EBPbeta activates E2F-regulated genes in vivo via recruitment of the coactivator CREB-binding protein/P300.
The E2F transcription factors play an essential role in regulating the G(1)- to S-phase transition of the cell cycle. Previous studies have identified the importance of interactions between E2Fs and other transcription factors as a mechanism for transcriptional control of a subset of E2F regulated target genes. However, the mechanisms responsible for E2F target gene specificity remain incompletely understood. Here we report that in a mammalian in vivo model of synchronized proliferation, C/EBPbeta occupancy on the promoters of E2F-regulated growth-related genes increases as a function of cell cycle progression. C/EPBbeta binding to these promoters is associated with recruitment of the coactivator CBP/p300, histone H4 acetylation, and maximal activation of E2F target genes. Moreover, binding of CBP/p300 to E2F targets is markedly reduced in C/EBPbeta null mice, resulting in reduced expression of E2F regulated genes. These findings identify C/EBPbeta as a direct activator of E2F target genes in mammalian cell cycle progression through a mechanism that involves recruitment of CBP/p300. The demonstration of a functional link between C/EBPbeta and CBP/p300 for E2F target gene activation provides a potential mechanism for how coactivators such as CBP/p300 can be selectively recruited to E2F target genes in response to tissue-specific growth stimuli.
Wang
Haitao
H
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Larris
Brian
B
Peiris
T Harshani
TH
Zhang
Liping
L
Le Lay
John
J
Gao
Yan
Y
Greenbaum
Linda E
LE
D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D050684:E2F Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors / Q000378:metabolism*
D022782:CCAAT-Enhancer-Binding Protein-beta; D050684:E2F Transcription Factors; D006657:Histones; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors