The packaging of DNA into nucleosomes, the repeating unit of chromatin comprised of histones, essentially regulates all biological functions of DNA in eukaryotes. One emphasis of the lab is on transcriptional activation, specifically, studying how chromatin-mediated repression is overcome through histone modifications (for example, acetylation) and the disassembly of nucleosomes, a process termed chromatin remodeling. These studies focus on induction of the PHO5 promoter in response to phosphate limitation, a proven model system for investigating chromatin remodeling in the budding yeast S. cerevisiae. Yeast offers many experimental advantages, including ease in biochemical, genetic, and molecular approaches. We have also identified a novel role for cell cycle regulators in PHO5 transcription and are currently determining their regulatory functions. Another area of investigation concerns the role of epigenetic or post-replicative methylation of DNA in tumor progression. In a recent collaboration, we have discovered increased DNA methylation of a novel mammalian tumor suppressor gene that is associated with elevated invasiveness of breast cancer. Future studies will examine mechanisms of epigenetic silencing of this tumor suppressor in human breast cancer lines and patient tumor tissue. Both areas of study take advantage of our powerful population and single-molecule strategies (MAP and MAP-IT, respectively) for probing chromatin structure with DNA methyltransferases. |
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Associate Professor