SCIENCE AT THE EDGE SEMINAR Friday, 18 February 2011 at 11:30am Room 1400 Biomedical and Physical Sciences Bldg. Refreshments at 11:15 Speaker: Joan Conaway Stowers Institute for Medical Research Kansas City, MO Title: The Mediator of RNA Polymerase II Transcription: Links to Transcription Elongation and Leukemogenesis Abstract: Promoter proximal pausing by initiated RNA polymerase II (Pol II) and regulated release of paused polymerase into productive elongation has emerged as a major mechanism of transcription activation. Reactivation of paused Pol II has been shown to correlate with recruitment of a so-called Super-Elongation Complex or SEC that contains the transcription elongation factors ELL/EAF and P-TEFb, as well as a collection of additional proteins encoded by genes involved in translocations with the MLL gene in leukemia. Our lab has recently obtained evidence for a role of human Mediator in recruiting SEC and another ELL/EAF-containing complex to genes. I will present evidence that a conserved N-terminal domain in the Mediator subunit Med26 provides docking sites for ELL/EAF, P-TEFb, and associated proteins as well as the general initiation factor TFIID. In addition, I will present evidence consistent with the model that Med26 may function as a molecular switch that interacts first with the Pol II initiation complex through direct interactions with TFIID and then "exchanges" TFIID for complexes containing elongation factors ELL/EAF and P-TEFb to facilitate the transition of Pol II into the elongation stage of transcription.