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2014-02

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cc-by-nc (c) Subtil-Rodríguez, Alicia et al., 2014
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/111087

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

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https://doi.org/10.1093/nar/gkt1161

Abstract

The 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.

Subject

Cromatina, Transcripció genètica, Fixació de proteïnes, Cicle cel·lular, Proliferació cel·lular, Histones

Subject (English)

Chromatin, Genetic transcription, Protein binding, Cell cycle, Cell proliferation, Histones

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Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Fonaments Clínics)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citation

SUBTIL-RODRÍGUEZ, Alicia, et al. The chromatin remodeller CHD8 is required for E2F-dependent transcription activation of S-phase genes. Nucleic Acids Research. 2014. Vol. 42, num. 4, pags. 2185-2196. ISSN 0305-1048. [consulted: 15 of August of 2026]. Available at: https://hdl.handle.net/2445/111087

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