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” Cell Cycle Transcriptional Regulation: Promoter Occupancy and Transcript Dynamics”
25 April 2013 from 4:00 PM to 5:00 PM
201 Thomas Bldg.
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Prevailing dogma holds that cyclin/CDK complexes are master regulators of cell cycle progression generally, and cell cycle transcription in particular.  However, in collaboration with Steve Haase, we demonstrated that periodic cell cycle transcription occurs even in yeast cells that completely lack B-cyclins (Orlando et al., Nature 2008).  Our hypothesis is that periodic transcription can arise from a transcriptional regulatory network exhibiting inherently periodic dynamics.  In this talk, I will describe two of our computational modeling efforts to better understand how this transcriptional regulatory network operates during the cell cycle.  First, we present COMPETE, a model that allows multiple DNA-binding factors, each at different concentrations, to compete with one another for binding sites along the genome.  The result is an occupancy profile, a probabilistic description of the DNA occupancy of each factor at each position along the genome, which provides a more mechanistic understanding of the dynamics of promoter occupancy during the cell cycle.  Second, we deconvolve population-level mRNA expression data, revealing transcript dynamics with markedly increased dynamic range and temporal resolution.  The fact that our model is based on a branching process allows us to identify genes that are expressed in a daughter-specific manner.