My lab is interested in understanding how one genome “encodes” multiple genetic programs to instruct formation of many distinct types of cells. Because gene transcription by RNA polymerase II (Pol II) is a critical step in controlling genetic programs, we are especially curious to learn the mechanisms of how Pol II transcription is globally regulated in different cell types.
It has long been thought that genes are activated primarily through binding of Pol II to their corresponding promoters. However, promoters of many genes contain high levels of Pol II, but do not necessarily show high levels of activity. On these genes, Pol II begins transcription but stops while synthesizing the first ~100 nucleotides of RNA. Recent studies showed that this promoter-proximal Pol II pausing is widespread in eukaryotes and that the release of paused Pol II into productive mRNA synthesis may regulate many genes, including those involved in cell differentiation, development, and response to stimuli.
How does Pol II transcription coordinate genetic programs? Our working hypothesis is that promoter-proximal Pol II pausing establishes transcriptional programs across the genome in response to other epigenetic and environmental cues. We utilize the latest Next-Generation sequencing approaches to map the genome-wide dynamics of paused Pol II during differentiation of stem cells and in cancer progression.