Forum 05/29/2003

“Insights into the Mechanisms of Eukaryotic Transcription Initiation and Regulation”

Michael Buchmeier, Professor – Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA

Cryo-electron microscopy and single particle analysis techniques are being used to conduct structural studies of the eukaryotic transcription machinery.  Using RNA polymerase II as a starting point, we are working to characterize the structure of the entire preinitiation complex, an assembly of polymerase and the general transcription factors that forms at a promoter to initiate transcription.  Combining information from intermediate-resolution cryo-EM maps with high-resolution x-ray structures of the polymerase and individual transcription factors has provided insight into the initiation mechanism.  Characterization of the Mediator coactivator and its interaction with the preinitiation complex indicates how regulatory information might be conveyed to the basal transcription machinery.  A high degree of conservation in basic aspects of transcription initiation and regulation is suggested by comparison with results from studies in bacteria.