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Étude des interactions entre le Médiateur et les facteurs généraux de la transcription par l'ARN polymérase II.

Abstract : In eukaryotes, RNA polymerase II (Pol II) is responsible for the transcription of coding genes and a large number of non-coding RNAs. The first step in transcription activation is the recognition of DNA motifs by activators that trigger the recruitment of co-activators, general transcription factors (GTFs) and ultimately Pol II to form a preinitiation complex (PIC). During my thesis we focused our study on the Mediator, a multiprotein complexe that plays a critical role in this process. We found different interactions between the Mediator and transcription factors that inform how it could influence the transcription initiation. First, we discovered a genetic interaction between MED31 that encodes the most conserved Mediator subunit and DST1 that encode the elongation factor TFIIS. Surprisingly, we revealed a new role for TFIIS which acts in conjunction with Mediator during transcription initiation to recruit PolII on promoter. Then, we identified a direct interaction between Med11 head Mediator subunit and Rad3 TFIIH subunit. We explored the significance of this interaction and those of Med11 with Med17 and Med22 head module subunits and found that impairing these interactions could differentially affect the recruitment of TFIIH, TFIIE and Pol II in PIC or destabilize the association of TFIIH modules. We also found that a med11 mutation that altered promoter occupancy by TFIIK kinase module of TFIIH reduced Pol II CTD serine 5 phosphorylation. We conclude that the Mediator head module plays a critical role in TFIIH, TFIIE and PolII recruitment in PIC. Altogether, these results suggest a branched assembly pathway in PIC formation.
Keywords : Mediator
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https://tel.archives-ouvertes.fr/tel-00331815
Contributor : Cyril Esnault <>
Submitted on : Friday, October 17, 2008 - 6:06:29 PM
Last modification on : Friday, September 11, 2015 - 9:59:07 AM
Long-term archiving on: : Saturday, November 26, 2016 - 2:20:03 AM

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  • HAL Id : tel-00331815, version 1

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Cyril Esnault. Étude des interactions entre le Médiateur et les facteurs généraux de la transcription par l'ARN polymérase II.. Biochimie [q-bio.BM]. Université Paris Sud - Paris XI, 2007. Français. ⟨tel-00331815⟩

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