Functional interplay between Mediator and TFIIB in preinitiation complex assembly in relation to promoter architecture

Thomas Eychenne (1, 2) , Elizaveta Novikova (1, 2) , Marie-Bénédicte Barrault (1, 2) , Olivier Alibert (3) , Claire Boschiero (4, 1, 2) , Nuno Peixeiro (1, 2) , David Cornu (5) , Virginie Redeker (6, 7) , Laurent Kuras (2) , Pierre Nicolas (7) , Michel Werner (1, 2) , Julie Soutourina (1, 2)

1 IBITECS - Institut de Biologie et de Technologies de Saclay
2 I2BC - Institut de Biologie Intégrative de la Cellule
3 LEFG - Laboratoire d'Exploration Fonctionnelle des Génomes
4 SBIGeM - Service de Biologie Intégrative et Génétique Moléculaire
5 SICaPS - SICaPS
6 NeuroPSI - Institut des Neurosciences Paris-Saclay
7 MaIAGE - Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas]

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.

Mots clés: Mediator; RNA polymerase II transcription; preinitiation complex; promoter architecture; RNA-POLYMERASE-II; IN-VIVO; INITIATION COMPLEX; ACTIVATION; YEAST; ORGANIZATION; SUBUNIT; GENOME

Mots clés: TFIIB; Saccharomyces cerevisiae; TRANSCRIPTION FACTOR TFIIB; RECRUITMENT

Domaines: Neurobiologie; Psychologie et comportements; Sciences cognitives

Thomas Eychenne, Elizaveta Novikova, Marie-Bénédicte Barrault, Olivier Alibert, Claire Boschiero, et al.. Functional interplay between Mediator and TFIIB in preinitiation complex assembly in relation to promoter architecture. Genes and Development, 2016, 30 (18), pp.2119 - 2132. ⟨10.1101/gad.285775.116⟩. ⟨hal-01405672⟩