Functional analysis of the transcriptional promoter for the CYP1A1 gene.
In mouse hepatoma cells, the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases the transcription rate of the CYP1A1 gene, which encodes a cytochrome P-450 enzyme. In this study, we analyzed the DNA region immediately upstream of the CYP1A1 gene. A domain that extends upstream to nucleotide--166 was found to function as a transcriptional promoter. The promoter was silent when uncoupled from the dioxin-responsive enhancer located farther upstream. DNase footprinting experiments indicated that nuclear proteins interact with distinct domains of the promoter in a TCDD-independent fashion. Mutational analyses indicated that the CYP1A1 promoter contains at least three functional domains, including a TATAAA sequence, a CCAAT box transcription factor/nuclear factor I-like recognition motif, and a guanine-rich G box.
Department of Pharmacology, Stanford University School of Medicine, California 94305.
K W
KW
Jones
J P
JP
Whitlock
D000818:Animals; D001665:Binding Sites; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004252:DNA Mutational Analysis; D004742:Enhancer Elements, Genetic; D015971:Gene Expression Regulation, Enzymologic; D008114:Liver Neoplasms, Experimental; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000072317:Polychlorinated Dibenzodioxins; D014157:Transcription Factors; D003577:Cytochrome P-450 Enzyme System