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A genomic study of the role of the Mediator of transcriptional regulation, carried out by a SBIGeM team, shows that this multiprotein complex coordinate the multiple stages of the setting up of the transcriptional machinery in vivo.
Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation in vivo at the genome level after a transfer to a non-permissive temperature for 45 minutes. The effect of a yeast mutation proposed to be equivalent to the human Med17-L371P responsible for infantile cerebral atrophy was also analyzed. The ChIP-seq results demonstrate that med17mutations differentially affected the global presence of several PIC components including Mediator, TBP, TFIIH modules and Pol II. Our data show that Mediator stabilizes TFIIK kinase and TFIIH core modules independently, suggesting that the recruitment or the stability of TFIIH modules is regulated independently on yeast genome. We demonstrate that Mediator selectively contributes to TBP recruitment or stabilization to chromatin. This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway.
Eyboulet F., Wydau-Dematteis S., Eychenne T., Alibert O., Neil H., Boschiero C., Nevers M.-C., Volland H., Cornu D., Redeker V., Werner M., & Soutourina J. (2015) Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo. Nucleic Acids Research, 43(19), 9214-31 http://dx.doi.org/10.1093/nar/gkv782
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.