Nancy Bigley (Committee Member), Khalid Elased (Committee Member), Courtney Sulentic (Advisor)
Master of Science (MS)
2,3,7,8-Tetrachlordibenzo-p-dioxin (TCDD) is a potent toxin which inhibits the antibody response of B cells. The 3'IgHRR which is involved in transcriptional regulation of the heavy-chain polypeptide of antibodies is inhibited by TCDD. The hs1,2 enhancer region, isolated from the 3'IgHRR, is also inhibited while the isolated hs4 is activated by TCDD. This project sought to determine if that dichotomy in effects results from interactions at enhancer-specific binding sites for AhR, thought to mediate transcriptional effects of TCDD, and NFκB, a transcription factor involved in B cell activation. Here, I report a difference in the effect of TCDD on transcriptional activity of the 3'IgHRR and the isolated hs3b/hs4 enhancer pair, in the context of chromatin. I also demonstrate reduced binding of proteins to the hs1,2 and hs4 enhancer sequences containing both AhR and NFκB binding sites compared to single site sequences, suggesting that an interaction between the proteins alters their binding to the enhancers.
Department or Program
Department of Pharmacology and Toxicology
Year Degree Awarded
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