Aryl hydrocarbon receptor-mediated regulation of gene expression in embryonic stem cells

grantor: University of TorontoThe aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that plays a key role in mediating the toxicity of various environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-'p'-dioxin (TCDD). In its native form the AHR resides in the cytoplasm of the cell and upon ligand binding to the receptor, a series of events is triggered that ultimately results in the altered expression of several genes. TCDD is a potent teratogen and developmental toxicant in several species. The mechanisms by which these adverse events are induced by TCDD remain unclear, but it is thought that the alteration in the expression of these genes particularly during development contributes to the toxicities observed. In the current study, I employed embryonic stem cells (ES R1), totipotent cells derived from mouse blastocysts, in conjunction with gene trap methodology to explore the AHR-mediated regulation of gene expression in the ES R1 cells to further understand the underlying mechanism of AHR-mediated teratogenesis. (Abstract shortened by UMI.)M.Sc