Abstract
RNA Polymerase II (Pol II) is the molecular machine that transcribes all the protein-encoding mRNAs as well as a spectrum of non-coding regulatory RNAs. The distribution of Pol II reveals not only location and levels of transcription of these transcribed genes, but also the distinctive patterns of divergent transcription that can be used to identify the active promoters and enhancers that regulate these genes. Moreover, by monitoring changes in the distribution of Pol II across genomes in response either to regulatory signals and to directed perturbations of transcription factors, the distinct steps in transcription that are regulated can be elucidated. With increasing positional and temporal resolution provided by new, genome-wide nuclear run-on and chromatin assays, like GRO-seq, PRO-seq, and GRO-cap, the speaker and his collaborators are able to gain critical insights into the mechanisms governing how RNA polymerases initiate and elongate through transcription units and how these processes are regulated. Moreover, the genome-wide patterns of regulated transcription provide insight to the networks of gene regulation and the biology of the stress response.
In this presentation, the speaker will provide a genome-wide view of the rapid and dramatic changes in transcription that accompany the heat shock stress response in both Drosophila and mammals. The heat shock model for studying transcription regulation has provided seminal insights into regulatory mechanisms in earlier, focused-gene studies. The highly-sensitive, genome-wide assays, which produce an immediate readout of transcription, have provided a host of new insights to stress regulation at the transcriptional level. It is found that promoter-proximal paused Pol II has a critical role for genes activated immediately upon heat shock and specific factors, such as GAGA Factor (GAF), are required for the earliest steps in transcription of creating or maintaining paused Pol II. The release of paused-Pol II into productive elongation is in turn upregulated by a group of transcription factors, such as HSF1, that bind to promoters and enhancers in response to heat shock. Finally, the speaker will describe a genome-wide nuclear run-on assay called CRO-seq that can be conveniently applied to intact tissues, and its application to characterizing primary human brain cancers.
About the speaker
Prof John Lis obtained his BS in Chemistry from Fairfield University in 1970 and PhD in Biochemistry from Brandeis University in 1975. He then proceeded with his postdoctoral work focused on Drosophila gene regulation and chromosome structure at Stanford University and joined Cornell University as an Assistant Professor in 1978. He is currently the Barbara McClintock Professor of Molecular Biology and Genetics in Cornell University.
Prof Lis’s research developed and used a variety of strategies to study the structure of promoters and genes and the mechanisms of their regulation in living cells. His main model system has been the heat shock genes. These genes can undergo a 200-fold activation of transcription in response to small change in temperature and other cellular stresses.
Prof Lis received the US National Institutes of Health MERIT Award in 1995. He was also elected a fellow of the American Association for the Advancement of Science, the American Academy of Arts and Sciences and a member of the US National Academy of Sciences.
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