RNA polymerase II transcription initiation in holo-TFIID-depleted mouse embryonic stem cells

RNA聚合酶II在全TFIID耗尽的小鼠胚胎干细胞中的转录起始

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作者:Vincent Hisler, Paul Bardot, Dylane Detilleux, Andrea Bernardini, Matthieu Stierle, Emmanuel Garcia Sanchez, Claire Richard, Lynda Hadj Arab, Cynthia Ehrhard, Bastien Morlet, Yavor Hadzhiev, Matthieu Jung, Stéphanie Le Gras, Luc Négroni, Ferenc Müller, László Tora, Stéphane D Vincent

Abstract

The recognition of core promoter sequences by TFIID is the first step in RNA polymerase II (Pol II) transcription initiation. Metazoan holo-TFIID is a trilobular complex, composed of the TATA binding protein (TBP) and 13 TBP-associated factors (TAFs). Why and how TAFs are necessary for the formation of TFIID domains and how they contribute to transcription initiation remain unclear. Inducible TAF7 or TAF10 depletion, followed by comprehensive analysis of TFIID subcomplex formation, chromatin binding, and nascent transcription in mouse embryonic stem cells, result in the formation of a TAF7-lacking TFIID or a minimal core-TFIID complex, respectively. These partial complexes support TBP recruitment at promoters and nascent Pol II transcription at most genes early after depletion, but importantly, TAF10 is necessary for efficient Pol II pausing. We show that partially assembled TFIID complexes can sustain Pol II transcription initiation but cannot replace holo-TFIID over several cell divisions and/or development.

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