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Biowulf Seminar: The Kinetics of Gene Transcription
Tuesday, February 4, 2020,
11:00:00 AM Time displayed is Eastern Time, Washington DC Local
Transcriptional regulation in metazoans occurs through long-range genomic contacts between enhancers and promoters, and most genes are transcribed in episodic ‘‘bursts’’ of RNA synthesis. Transcription can be affected by perturbations to transcription factors and nuclear architecture. To understand the relationship between these phenomena and the dynamic regulation of genes in response to upstream signals, a wide range of experimental methods are used from in vitro measurements of gene expression in a large number of cells to live-cell RNA imaging in single cells. A means to synthesize this data and dissect the mechanism of gene transcription is to develop and fit a fully stochastic kinetic model of transcription kinetics and RNA abundance. I will present ongoing work of such a model that can explain a wide range of phenomena including the dose response curve for hormone-induced gene induction and the heterogeneity in protein levels in human tissue. Most recently, we have applied the model to single cell RNA measurements of the entire human genome to characterize the effect of promoter-enhancer contacts. I will show how harnessing the full capabilities of Biowulf is required to perform the computations on such a large number of genes.