Mammalian Gene Regulation
We are examining the generality of models and exploring new hypothesis using both focused studies on mammalian heat shock genes and genome-wide analysis of mouse and human gene regulation. The focused studies of mouse heat shock genes are taking advantage of cell lines that are knock-outs for the master regulators HSF1 and HSF2. Genome-wide assays are defining the complete regulatory networks of the heat shock response and the relationship of the HSF-regulated pathways to cancer.
Complete transcriptional patterns revealed by our Global Run-On (GRO-seq) in Drosophila and well-studied mammalian cell lines are assessing the generality of promoter-proximal pausing as a mechanism of gene regulation. These and additional studies are also allowing us to investigate of the underlying mechanisms of this regulation.