E2F mediates cell cycle-dependent transcriptional repression in vivo by recruitment of an HDAC1/mSin3B corepressor complex

摘要: Despite biochemical and genetic data suggesting that E2F pRB (pocket protein) families regulate transcription via chromatin-modifying factors, the precise mechanisms underlying gene regulation by these protein have not yet been defined in a physiological setting. In this study, we investigated promoter occupancy wild-type pocket protein-deficient primary cells. We show corepressor complexes consisting of histone deacetylase (HDAC1) mSin3B were specifically recruited to endogenous E2F-regulated promoters quiescent These dissociated from once cells reached late G1, coincident with activation. Interestingly, recruitment HDAC1 depended absolutely on p107 p130, required an intact E2F-binding site. contrast, certain did require or can occur E2F-dependent -independent mechanisms. Remarkably, loss had no effect recruitment. p107/p130 deficiency triggered dramatic E2F4 nuclear localization as well transcriptional derepression, which is suggested nucleosome mapping studies be result localized hyperacetylation nucleosomes proximal sites. Taken together, findings p130 escorts into nucleus and, together contain and/or HDAC1, directly represses target genes withdraw cell cycle.