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Title

The chromatin remodeller CHD8 is required for E2F-dependent transcription activation of S-phase genes

AuthorsSubtil-Rodríguez, Alicia ; Vázquez-Chávez, Elena; Ceballos-Chávez, María ; Rodríguez-Paredes, Manuel ; Martín-Subero, José Ignacio; Esteller, Manel; Reyes, José C.
Issue Date21-Nov-2013
PublisherOxford University Press
CitationNucleic Acids Research 42(4): 2185- 2196 (2014)
AbstractThe precise regulation of S-phase-specific genes is critical for cell proliferation. How the repressive chromatin configuration mediated by the retinoblastoma protein and repressor E2F factors changes at the G1/S transition to allow transcription activation is unclear. Here we show ChIP-on-chip studies that reveal that the chromatin remodeller CHD8 binds ∼2000 transcriptionally active promoters. The spectrum of CHD8 target genes was enriched in E2F-dependent genes. We found that CHD8 binds E2F-dependent promoters at the G1/S transition but not in quiescent cells. Consistently, CHD8 was required for G1/S-specific expression of these genes and for cell cycle re-entry on serum stimulation of quiescent cells. We also show that CHD8 interacts with E2F1 and, importantly, loading of E2F1 and E2F3, but not E2F4, onto S-specific promoters, requires CHD8. However, CHD8 recruiting is independent of these factors. Recruiting of MLL histone methyltransferase complexes to S-specific promoters was also severely impaired in the absence of CHD8. Furthermore, depletion of CHD8 abolished E2F1 overexpression-dependent S-phase stimulation of serum-starved cells, highlighting the essential role of CHD8 in E2F-dependent transcription activation
Publisher version (URL)http://dx.doi.org/10.1093/nar/gkt1161
URIhttp://hdl.handle.net/10261/123631
DOI10.1093/nar/gkt1161
Identifiersdoi: 10.1093/nar/gkt1161
issn: 1362-4962
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