The DNA recognition site for the dioxin-Ah receptor complex. Nucleotide sequence and functional analysis.
The environmental contaminant 2,3,7,8-tetra-chlorodibenzo-p-dioxin produces its biological effects by binding to an intracellular protein (the Ah receptor). The dioxin-Ah receptor complex activates cytochrome P1-450 gene transcription by interacting with dioxin-responsive enhancers. Here, we report that the dioxin-Ah receptor complex binds to DNA containing the "core" sequence 5'-TA/TGCGTG-3', which is present in each of three receptor-dependent enhancers. Functional analyses indicate that binding of the liganded Ah receptor to the core sequence fails to generate an active enhancer and that nucleotides flanking the core sequence must contribute to enhancer function and dioxin action.
Denison
M S
MS
Department of Pharmacology, Stanford University School of Medicine, California 94305.
Fisher
J M
JM
Whitlock
J P
JP
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics; D004247:DNA / Q000235:genetics*; D004147:Dioxins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D004790:Enzyme Induction; D005786:Gene Expression Regulation; D008114:Liver Neoplasms, Experimental; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010957:Plasmids; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000235:genetics* / Q000378:metabolism
D004147:Dioxins; D015345:Oligonucleotide Probes; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D004247:DNA; D003577:Cytochrome P-450 Enzyme System