Computational Advances in Elucidating Cell Cycle Transcriptional Regulation

Alexander Hartemink
Duke University
Computer Science

Prevailing dogma holds that cyclin/CDK complexes are master regulators of cell cycle progression generally, and cell cycle transcription in particular. However, in collaborative work with Steve Haase, we have 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 arises 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 deconvolve population-level mRNA expression data to reveal transcript dynamics with markedly increased dynamic range and temporal resolution. Second, we adopt a systems perspective to model the competitive binding of multiple factors to the genome, with an eye toward a more mechanistic understanding of the dynamics of promoter occupancy during the cell cycle.

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