MBGE SEMINAR by Murat Cevher

Time: 14:30
Location: SCI 103

Speaker          :
Murat Cevher, Bilkent University

Title                : Using the Mediator to selectively regulate activated target genes

Date                : December 5, 2019, Thursday
Time               : 14:30  
Cookie & Tea: 14:15 SCI 103
Place               : SCI 103

Abstract         : Mediator is the most critical coactivator complex that is involved in the regulation of most (if not all) Pol II target genes. It is composed of 30-tightly associated subunits with a total molecular weight of 2MDa in humans. Mediators main function comes from bridging the enhancer bound activators with the promoter associated general transcriptional machinery including Pol II. Mediator also properly modulates the pre-initiation complex assembly at TATA promoters by recruiting some of the general transcriptional machinery including the Pol II.  Here for the first time, we report functionally, mechanistically and architecturally in detail, how the Mediator associates with the activator estrogen receptor alpha, recruit Pol II and other general transcription factors (GTFs) to TATA promoters to mediate transcription and moreover understand under what conditions this gene activation is repressed. By reconstituting all 30-subunits of the Mediator using the multibac baculovirus expression system, we are now in a better position of solving activator mediated activation of target genes via the Mediator complex. More importantly, as Mediator is critical at the subunit level, we are now in a better position to specifically inhibit activators of interest as long as we know which subunit of the Mediator they interact with.  This way, the Mediator could be used for therapeutics as it has a specificity angle towards activators.