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SUMMARY:Molecular mechanisms of Mediator complex recruitment by transcript
 ion factors. - Alexis Verger from Institut de Recherche Interdisciplinaire
 \, Université de Lille 
DTSTART:20140508T133000Z
DTEND:20140508T143000Z
UID:TALK51133@talks.cam.ac.uk
CONTACT:Caroline Newnham
DESCRIPTION:MED25 is a subunit specific to higher eukaryote Mediator compl
 ex\, an essential component of the RNA polymerase II general transcription
 al machinery. Mediator plays major roles in both basal and activated trans
 cription by interacting with transactivation domains (TADs) of transcripti
 onal activators on the one hand and the RNA polymerase II on the other han
 d. We recently demonstrated that the TAD of the PEA3 subfamily of ETS tran
 scription factors (ERM\, ETV1 and PEA3) directly interacts with the ACID/P
 TOV domain of the Mediator complex subunit MED25. We have determined the s
 tructure of the ACID/PTOV domain by NMR spectroscopy that consists of a cl
 osed β-barrel with seven strands and three α-helices\, an architecture s
 howing similarities to that of the SPOC domain-like superfamily. The inter
 action between ERM TAD and MED25 ACID/PTOV domain was characterized by iso
 thermal titration calorimetry (ITC)\, fluorescence polarization (FP) and N
 MR. The ERM TAD is disordered in solution but has a propensity to adopt lo
 cal transient conformations suggesting a folding upon binding mechanism of
  ERM to MED25. The relevance of this binding mode for ERM compared to the 
 binding of MED25 to the TAD of the herpes simplex virus transcription fact
 or VP16 will be discussed. Moreover\, reporter-gene based assays and siRNA
 -mediated knockdown approaches revealed that MED25 is important for full a
 ctivation of ERM-mediated transcription and that MED25 ACID/PTOV domain se
 rves as a docking site on Mediator for the PEA3 subfamily transcriptional 
 activation domain. Finally\, our recent efforts to better understand struc
 ture and function of higher eukaryotes-specific Mediator subunits will be 
 presented. 
LOCATION:Part II Room\, Department of Genetics
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