The DNA recognition site for the dioxin-Ah receptor complex. Nucleotide sequence and functional analysis

• Published in: The Journal of biological chemistry 1988-11, Vol.263 (33), p.17221-17224
• Main Authors: Denison, M S, Fisher, J M, Whitlock, J P
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; Cell Line; Chemical and industrial products toxicology. Toxic occupational diseases; Cytochrome P-450 Enzyme System - biosynthesis; Cytochrome P-450 Enzyme System - genetics; Dioxins - metabolism; DNA - genetics; Enhancer Elements, Genetic; Enzyme Induction; Gene Expression Regulation; Liver Neoplasms, Experimental; Medical sciences; Mice; Molecular Sequence Data; Oligonucleotide Probes; Plasmids; Polychlorinated Dibenzodioxins - metabolism; Polychlorinated Dibenzodioxins - pharmacology; Protein Binding; Receptors, Aryl Hydrocarbon; Receptors, Drug - genetics; Receptors, Drug - metabolism; Toxicology; Various organic compounds
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)77819-3

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.