2,3,7,8-Tetrachlorodibenzo-p-dioxin-inducible, Ah receptor-mediated bending of enhancer DNA.
The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin produces its biological effects by binding to an intracellular protein, the Ah receptor. The liganded receptor activates transcription by binding to a specific recognition motif within a dioxin-responsive enhancer upstream of the target CYP1A1 gene. Here, we have used gel retardation to analyze the interaction between the liganded Ah receptor and five circularly permuted DNA fragments that contain a receptor recognition motif. Our findings indicate that the binding of the liganded receptor to its recognition motif bends the DNA at (or near) the site of the protein-DNA interaction. This observation implies that Ah receptor-induced DNA distortion may contribute to the activation of CYP1A1 transcription by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Elferink
C J
CJ
Department of Pharmacology, Stanford University, California 94305.
Whitlock
J P
JP
D000345:Affinity Labels; D000818:Animals; D001665:Binding Sites; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004247:DNA / Q000378:metabolism*; D004270:DNA, Circular / Q000378:metabolism; D004147:Dioxins / Q000494:pharmacology*; D004587:Electrophoresis, Agar Gel; D004742:Enhancer Elements, Genetic; D005822:Genetic Vectors; D008114:Liver Neoplasms, Experimental; D051379:Mice; D009690:Nucleic Acid Conformation; D010957:Plasmids; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000345:Affinity Labels; D004270:DNA, Circular; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; C056902:2-iodo-7,8-dibromodibenzo-1,4-dioxin; D004247:DNA; D003577:Cytochrome P-450 Enzyme System