Control of cytochrome P1-450 gene expression by dioxin.
The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may produce its effects by altering gene expression in susceptible cells. In mouse hepatoma cells, TCDD induces the transcription of the cytochrome P1-450 gene, whose product, aryl hydrocarbon hydroxylase, contributes both to the detoxification and to the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons. A DNA fragment containing sequences flanking the 5' end of the cytochrome P1-450 gene was isolated and analyzed. This DNA fragment contains a cis-acting control element with at least three functional domains: a putative promoter, an inhibitory domain upstream from the promoter that blocks its function, and a TCDD-responsive domain still farther (1265 to 1535 base pairs) upstream of the promoter. These findings, together with results from earlier studies, imply that transcription of the cytochrome P1-450 gene is under both positive and negative control by at least two trans-acting regulatory factors.
D000123:Acetyltransferases / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004274:DNA, Recombinant; D004147:Dioxins / Q000494:pharmacology*; D004790:Enzyme Induction; D005786:Gene Expression Regulation / Q000187:drug effects*; D005809:Genes, Regulator; D008114:Liver Neoplasms, Experimental; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D004274:DNA, Recombinant; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D014157:Transcription Factors; D003577:Cytochrome P-450 Enzyme System; D000123:Acetyltransferases; D015500:Chloramphenicol O-Acetyltransferase