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(P586) Sequence comparisons of the CYP1A promoter of AHR ligand-resistant and -responsive killifish (Fundulus heteroclitus) populations.
Arzuaga, Xabier*,1, Elskus, Adria, 1 University of Kentucky, Lexington, KY, USA
ABSTRACT- Xenobiotic-carcinogenic compounds such as 2,3,7,8-tetraclorodibenzo-p-dioxin, benzo-a-pyrene and coplanar polychlorinated biphenyls (PCBs) are inducers of metabolizing enzymes that form part of the aryl hydrocarbon receptor (AHR) gene battery. One of these enzymes is Cytochrome P450 1A (CYP1A). Killifish (Fundulus heteroclitus) populations chronically exposed to these compounds have developed heritable resistance to their toxic effects and to induction of CYP1A. One possible mechanism underlying CYP1A resistance may be variations in the regulatory sequences of the promoter region of this gene leading to suppression of CYP1A expression in resistant fish. We amplified a ~2kb region of the CYP1A promoter of fish from several contaminated and reference populations. Preliminary sequence analysis revealed complete DNA binding motifs for the transcription factors: AHR, SP-1, and CREB, and motifs very similar to the recognition sequences for the transcription factors HF-1, NF-kB and AP-1 in the promoter of all killifish populations examined, regardless of pollutant exposure history. Further sequence analysis will reveal whether critical differences exist in binding sites for transcription activators and repressors, the relative position of regulatory sequences amongst populations, and the possible role of epigenetic factors in CYP1A regulation (e.g. silencing via DNA methylation).
Key words: Resistance, XRE, TCDD, fish
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