Journal
GENES & DEVELOPMENT
Volume 30, Issue 18, Pages 2119-2132Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.285775.116
Keywords
Mediator; RNA polymerase II transcription; TFIIB; preinitiation complex; Saccharomyces cerevisiae; promoter architecture
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Funding
- Agence Nationale de la Recherche [ANR-08-BLAN-0229, ANR 11 BSV8 020 01, ANR-14-CE10-0012-01]
- Fondation ARC [SL 2201130607079]
- Fondation pour la Recherche Medicale [FDT20150531985]
- Agence Nationale de la Recherche (ANR) [ANR-08-BLAN-0229] Funding Source: Agence Nationale de la Recherche (ANR)
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Mediator is a large coregulator complex conserved from yeast to humans and involved in many human diseases, including cancers. Together with general transcription factors, it stimulates preinitiation complex (PIC) formation and activates RNA polymerase II (Pol II) transcription. In this study, we analyzed how Mediator acts in PIC assembly using in vivo, in vitro, and in silico approaches. We revealed an essential function of the Mediator middle module exerted through its Med10 subunit, implicating a key interaction between Mediator and TFIIB. We showed that this Mediator TFIIB link has a global role on PIC assembly genome-wide. Moreover, the amplitude of Mediator's effect on PIC formation is gene-dependent and is related to the promoter architecture in terms of TATA elements, nucleosome occupancy, and dynamics. This study thus provides mechanistic insights into the coordinated function of Mediator and TFIIB in PIC assembly in different chromatin contexts.
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