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Scientific result | DNA | Health ＆ life sciences
An in vivo, in vitro and in silico study of the Mediator of Transcriptional Regulation has shown how the function of this multiprotein complex is coordinated with another essential component of the transcription machinery, the TFIIB factor, and the architecture of the promoter. This study, led by SBIGeM, was conducted in collaboration with several other Research Teams (CNRS, CEA, INRA).
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.Read the French version.
Eychenne T., Novikova E., Barrault M.-B., Alibert O., Boschiero C., Peixeiro N., Cornu D., Redeker V., Kuras L., Nicolas P., Werner M., & Soutourina J. Functional interplay between Mediator and TFIIB in preinitiation complex assembly in relation to promoter architecture. (2016) Genes & Development, 30(18), 2119-2132 http://dx.doi.org/10.1101/gad.285775.116
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.