Djem Kissiov

kissiovd(at)berkeley.edu

Postdoctoral Researcher

Stochastic Bistable Switches in Developmental Gene Expression

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Cell fate decisions are defined by the implementation of cell type-specific gene expression programs. Gene expression decisions are inherently binary–a cell either expresses a gene or it does not. It has recently become clear that the two copies of a gene in diploid cells do not always come to the same decision, despite sharing a trans regulatory environment. While this was thought to be restricted to small subsets of autosomal genes (albeit a surprisingly large proportion of genes!), my graduate work provided evidence that all developmentally regulated genes may be subject to stochastic allelic regulation, to varying extents. That is, rather than provide a certainty of a given cell type-specific gene being expressed biallelically, a particular trans nuclear environment raises the probability of gene allele expression.

I am using both super resolution microscopy-based and high-throughput genetic screen-based approaches to uncover the molecular players that establish and maintain these probabilistic and binary expression states, along with nuclear factors that influence the likelihood of a gene allele falling under either the on or off state. Our hope is that by understanding the fundamental biochemistry of bistable states we will achieve a more complete picture of how cell type-specific gene expression programs are achieved by the developing organism.