Dioxin acts by altering the transcription of specific genes; the chemical serves as a prototype for environmental contaminants that elicit responses via receptor-dependent mechanisms. As a model response for studying dioxin action, we analyze the mechanism by which TCDD induces the transcription of the CYP1A1 gene. Cyp1A1 encodes cytochrome P450 1A1, a microsomal enzyme that oxygenates certain lipophilic aromatic hydrocarbons, such as the carcinogen benzo(a)pyrene, during their metabolic processing to water-soluble derivatives. We use mouse hepatoma cells as an experimental system, and our studies employ a variety of biochemical, genetic, and molecular biological techniques to analyze the mechanism of gene transcription and dioxin action. Our experiments have contributed to the elucidation of a novel transcriptional control system, which involves two regulatory bHLH/PAS proteins, a variety of protein-DNA interactions and protein-protein interactions, and alterations in chromatin structure. Our findings have generated new insights into the pathways by which cells respond to environmental stimuli by altering the expression of specific genes.
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[transcriptional control] [bHLH/PAS proteins] [protein-DNA interactions] [chromatin structure] [protein-protein interactions] [hypoxia-response genes]