It is becoming increasingly clear that a significant fraction of gene regulatory decisions are directed at RNA polymerase after transcription has initiated. Genes whose expression must change quickly are often found to bear an RNA polymerase which has started RNA synthesis but halted shortly afterward, within 50 nt of the start point. Among these genes are many proto-oncogenes, such as c-myc and c-fos, whose misregulation can have catastrophic effects on human health. The goal of this research is a deeper understanding of the molecular mechanisms by which RNA polymerase II establishes and maintains competence to continue RNA chain elongation. Questions to be addressed by this work include: Among the events which accompany the very first stages of transcription, which are critical to allow polymerase to escape its interaction with the promoter? How does the polymerase subsequently lock into the stable transcript-elongation state? In particular, what role does the RNA itself play in controlling this latter event? Does the RNA interact with a specific site on the polymerase, well upstream of the point of bond formation? Can template sequences be identified which make the RNA polymerase's transition from the initiating to the elongating state particularly difficult?
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