Mediator-dependent recruitment of TFIIH modules in preinitiation complex

被引:121
作者
Esnault, Cyril [1 ]
Ghavi-Helm, Yad [1 ]
Brun, Sylvain [1 ]
Soutourina, Julie [1 ]
Van Berkum, Nynke [2 ]
Boschiero, Claire [1 ]
Holstege, Frank [2 ]
Werner, Michel [1 ]
机构
[1] CEA, iBiTec S, F-91191 Gif Sur Yvette, France
[2] Univ Med Ctr Utrecht, Dept Physiol Chem, NL-3584 CG Utrecht, Netherlands
关键词
D O I
10.1016/j.molcel.2008.06.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In vitro, without Mediator, the association of general transcription factors (GTF) and RNA polymerase 11 (Pol II) in preinitiation complexes (PIC) occurs in an orderly fashion. In this work, we explore the in vivo function of Mediator in GTF recruitment to PIC. A direct interaction between Med11 Mediator head subunit and Rad3 TFIIH subunit was identified. We explored the significance of this interaction and those of Med11 with head module subunits Med17 and Med22 and found that impairing these interactions could differentially affect the recruitment of TFIIH, TFIIE, and Pol II in the PIC. A med11 mutation that altered promoter occupancy by the TFIIK kinase module of TFIIH genome-wide also reduced Pol 11 CTD serine 5 phosphorylation. We conclude that the Mediator head module plays a critical role in TFIIH and TFIIE recruitment to the PIC. We identify steps in PIC formation that suggest a branched assembly pathway.
引用
收藏
页码:337 / 346
页数:10
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