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

• Published in: Cell reports (Cambridge) 2024-10, Vol.43 (10), p.114791-114791, Article 114791
• Main Authors: Hisler, Vincent, Bardot, Paul, Detilleux, Dylane, Bernardini, Andrea, Stierle, Matthieu, Sanchez, Emmanuel Garcia, Richard, Claire, Arab, Lynda Hadj, Ehrhard, Cynthia, Morlet, Bastien, Hadzhiev, Yavor, Jung, Matthieu, Le Gras, Stéphanie, Négroni, Luc, Müller, Ferenc, Tora, László, Vincent, Stéphane D.
• Format: Article
• Language: English
• Subjects: Animal genetics; Animals; Biochemistry, Molecular Biology; Chromatin - metabolism; complex assembly; CP: Molecular biology; Development Biology; Genetics; Genomics; Life Sciences; Mice; mouse embryonic stem cells; Mouse Embryonic Stem Cells - metabolism; nascent transcription; Promoter Regions, Genetic - genetics; RNA polymerase II; RNA Polymerase II - metabolism; TAF10; TAF7; TATA binding protein; TATA-Binding Protein Associated Factors - genetics; TATA-Binding Protein Associated Factors - metabolism; TATA-Box Binding Protein - genetics; TATA-Box Binding Protein - metabolism; TBP; TBP-associated factor; TFIID; Transcription Factor TFIID - genetics; Transcription Factor TFIID - metabolism; Transcription Initiation, Genetic; Transcription, Genetic
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114791

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. [Display omitted] •TAF7 or TAF10 depletion leads to the formation of different partial TFIID complexes•Nascent Pol II transcription is not strongly affected in holo-TFIID-depleted cells•TBP is recruited at the promoter in holo-TFIID-depleted cells•Pol II pausing is affected in the absence of TAF10 Hisler et al. reveal that TAF7 and TAF10 depletion affects holo-TFIID sequential assembly, leading to the formation of partial TFIID complexes. Transcription is active and TBP is recruited at promoters when holo-TFIID is depleted. Partial TFIID complexes may sustain active transcription but cannot replace holo-TFIID over several cell divisions and/or development.