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oai:recercat.cat:2445/1110872025-11-20T13:51:27Zcom_2072_1057col_2072_478799col_2072_478824col_2072_478916col_2072_478917

The chromatin remodeller CHD8 is required for E2F-dependent transcription activation of S-phase genes Subtil-Rodríguez, Alicia Vázquez-Chávez, Elena Ceballos-Chávez, María Rodríguez-Paredes, Manuel Martín-Subero, José Ignacio Esteller, Manel Reyes, José C. Cromatina Transcripció genètica Fixació de proteïnes Cicle cel·lular Proliferació cel·lular Histones Chromatin Genetic transcription Protein binding Cell cycle Cell proliferation Histones 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. 2017-05-16T11:38:16Z 2017-05-16T11:38:16Z 2014-02 2017-05-16T11:38:17Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.1093/nar/gkt1161 Nucleic Acids Research, 2014, vol. 42, num. 4, p. 2185-2196 https://doi.org/10.1093/nar/gkt1161 cc-by-nc (c) Subtil-Rodríguez, Alicia et al., 2014 http://creativecommons.org/licenses/by-nc/3.0/es info:eu-repo/semantics/openAccess Oxford University Press Articles publicats en revistes (Ciències Fisiològiques)