C/EBPβ activates E2F-regulated genes in vivo via recruitment of the coactivator CREB-binding protein/p300

Haitao Wang, Brian Larris, T. Harshani Peiris, Liping Zhang, John Le Lay, Yan Gao, Linda E. Greenbaum

Research output: Contribution to journalArticle

34 Scopus citations

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 languageEnglish (US)
Pages (from-to)24679-24688
Number of pages10
JournalJournal of Biological Chemistry
Volume282
Issue number34
DOIs
StatePublished - Aug 24 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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