Abstract
The E2F transcription factors play an essential role in regulating the G1- 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/EBPβ occupancy on the promoters of E2F-regulated growth-related genes increases as a function of cell cycle progression. C/EPBβ 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/EBPβ null mice, resulting in reduced expression of E2F regulated genes. These findings identify C/EBPβ 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/EBPβ 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.
Original language | English (US) |
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Pages (from-to) | 24679-24688 |
Number of pages | 10 |
Journal | Journal of Biological Chemistry |
Volume | 282 |
Issue number | 34 |
DOIs | |
State | Published - Aug 24 2007 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology