RNA polymerase II transcription initiation in holo-TFIID-depleted mouse embryonic stem cells
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.
Authors
- Dylane Detilleux (ORCID: https://orcid.org/0000-0001-9193-7891)
- Matthieu Stierlé
- Bastien Morlet (ORCID: https://orcid.org/0000-0001-6058-7366)
- Làszlò Tora (ORCID: https://orcid.org/0000-0001-7398-2250)
- Paul Bardot
- Stéphane D. Vincent (ORCID: https://orcid.org/0000-0003-1638-9615)
- Claire Richard (ORCID: https://orcid.org/0000-0001-6520-5494)
- Matthieu Jung (ORCID: https://orcid.org/0000-0002-3272-7322)
- Luc Négroni (ORCID: https://orcid.org/0000-0002-6204-3917)
- Lynda Hadj Arab
- Stéphanie Le Gras (ORCID: https://orcid.org/0000-0001-6293-6507)
- Andrea Bernardini (ORCID: https://orcid.org/0000-0001-5082-5295)
- Vincent Hisler (ORCID: https://orcid.org/0000-0002-3483-4906)
- Yavor Hadzhiev (ORCID: https://orcid.org/0000-0002-1134-4904)
- Cynthia Ehrhard
- Emmanuel Garcia Sanchez
- Ferenc Müller
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut de génétique et de biologie moléculaire et cellulaire (FR)
- University of Birmingham (GB)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-09-30
- DOI
- https://doi.org/10.1016/j.celrep.2024.114791
- Citations
- 4
- Primary Topic
- CRISPR and Genetic Engineering
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- National Science Foundation
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale
- Université de Strasbourg
- National Institutes of Health