Mechanisms of Transcriptional Regulation in Drosophila & Mammalian Cells

Abstract

Transcription in higher eukaryotes is highly orchestrated at our ~20K mRNA encoding genes. The levels and cellular patterns of transcription of these genes respond to a spectrum of signals including those occurring in response to our normal program of development, in response to changes in nutrition and environment, and importantly, in response to infection and other disease states. These different regulatory signals target the activation of specific sets of genes at a pair of early steps in the transcription cycle, namely: Step 1) the recruitment of the transcription machine, RNA polymerase II (Pol II) to the promoter, which includes opening of chromatin and the initiation of Pol II and its rapid progression the promoter-proximal pause region; and Step 2) release of paused Pol II into  productive elongation. How specific transcription factors act on these distinct steps to integrate regulatory signals and control transcriptional output will be the focus of this seminar. While our initial work focused on heat shock genes as a model system, the development of genome-wide methods that are highly-sensitive and have base-pair resolution have shown the generality of early findings using the heat shock gene model.  I’ll end by briefly highlighting some of our past, and recently reinvigorated, microscopy efforts that examined transcription factors and Pol II during heat shock gene activation in real time in living polytene cells.

Publications :

-Wissink, EM, et al 2019 "Nascent RNA analyses: tracking transcription and its regulation. DOI : 10.1038/s41576-019-0159-6
-Tome, JM, et al 2018 "Single-molecule nascent RNA sequencing identifies regulatory domain architecture at promoters and enhancers. DOI : 10.1038/s41588-018-0234-5
-Zobeck, KL, et al 2010 "Recruitment timing and dynamics of transcription factors at the Hsp70 loci in living cells. DOI : 10.1016/j.molcel.2010.11.022