title: Transcriptional regulation of 3-methylcholanthrene-inducible P-450 gene responsible for metabolic activation of aromatic carcinogenes.
abstract: We have investigated the transcriptional regulation of 3-methylcholanthrene (3MC)-inducible P-450c gene which is involved in the metabolic activation of polycyclic aromatic carcinogens. Reverse genetic study using the fusion gene composed of the 5' upstream sequence of P-450c gene and the structure gene for bacterial chloramphenicol acetyltransferase (CAT) and a cultured cell line of Hepa-1 cells localized two kinds of cis-acting regulatory DNA elements. One is designated XRE or xenobiotic responsive element which is responsible for the inducibility of the gene and is distributed 5 times in the region from -3.0 to -0.5 kb. The other is BTE or basal transcription element whose deletion reduces a low level of the constitutive CAT expression to a background level, and which is localized immediately upstream of the TATA sequence. Both kinds of regulatory elements are necessary for a high level of inducible expression. Gel mobility shift assay strongly suggests that the binding protein to the XRE is an Ah receptor with a specific affinity for 3MC or 2,3,7,8,tetrachlorodibenzo-p-dioxin (TCDD). Without inducer treatment, cryptic form of the binding protein occurs only in the cytoplasm of the Hepa-1 cells. Upon treatment with the inducer, the cryptic form of the binding protein exhibits binding activity to XRE and, at the same time, translocates to the nuclei. The BTE-binding protein is an ubiquitous nuclear factor and its cDNA cloning reveals the DNA-binding feature with zinc finger motifs.
authors: Department of Chemistry, Faculty of Science, Tohoku University, Sendai, Japan.
authors: Y
authors: Y
authors: Fujii-Kuriyama
authors: K
authors: K
authors: Sogawa
authors: H
authors: H
authors: Imataka
authors: K
authors: K
authors: Yasumoto
authors: Y
authors: Y
authors: Kikuchi
authors: A
authors: A
authors: Fujisawa-Sehara
mesh_terms: D000818:Animals; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004742:Enhancer Elements, Genetic; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D008748:Methylcholanthrene / Q000494:pharmacology*; D008969:Molecular Sequence Data; D000072317:Polychlorinated Dibenzodioxins; D011401:Promoter Regions, Genetic; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D015534:Trans-Activators / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D015534:Trans-Activators; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D015500:Chloramphenicol O-Acetyltransferase