Role of eukaryotic transcription regulators in the regulation of stochastic gene expression

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The answer to the conundrum of how, when, and to what level genes of living organisms are regulated constitutes the key determinant of all biological species' propagation and evolution.  Hence any event that leads to the dysfunction of this regulation can inevitably promote diseases such as cancer.  In the last decade or so, colossal advances have been made in our understanding of the molecular mechanisms that control gene expression.  Gene-specific transcription factors need to access their regulatory targets in order to modulate the expression of genes.  To achieve this regulation, chromatin must first be appropriately remodeled to preset activation or repression states at a given gene.  The long-term goal of my laboratory is to understand how transcription factors function in a chromatin environment to elicit a transcription response under an appropriate physiological cue.Classical ways of studying the function of transcription factors in gene expression have used technologies that were aimed at measuring gene expression levels of a population of cells.  However, recent experiments have now shown that random fluctuations in gene expression occurred from cell to cell, therefore making cells prone to variability in cellular behavior.  Our work will now consist of studying the importance of various types of transcription factors (i.e. activators and coactivators), as well as histone modifications, in regulating gene expression in a 'cell-to-cell' context, and how that contributes to stochastic gene expression.  For this, we will make use of fluorescent reporter assays, coupled with genetic and chromatin immunoprecipitation approaches.    It is my firm belief that this research program will reveal important new mechanisms of gene regulation that occur within a population of cells.