Interdisciplinary Training

Eric Herbig

"Mechanism of Gene Specific Activator Function"

Transcription factors (TFs) bridge cellular signaling events and transcriptional regulation. They function by recruiting mega-Dalton sized complexes called Coactivators (CAs), which can alter chromatin state and direct functioning of RNA polymerase II and the general transcription factors. The molecular mechanisms governing TF-CA interactions are poorly understood. I hypothesize that these interactions will induce structural changes in both TFs and CA targets and that alterations in transcription factor structure will vary among binding partners. Further, I predict that these interactions will be driven by hydrophobic interactions and that spacing and number of hydrophobic residues will strongly affect conformational change and binding strength. To test these proposals, I am mapping the precise regions of contact between an activator and promoter bound CA complexes and will delimit the regions of CA subunits required for activator binding. I next aim to solve the first activator-CA complex high resolution structure. Finally, I will test the importance of this structure, using yeast molecular genetics.