Structure of the 5' flanking region of class 3 aldehyde dehydrogenase in the rat.
Class 3 aldehyde dehydrogenase (ALDH-3) is induced by exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and during chemical carcinogenesis. These inductions as well as the basal expression of ALDH-3 vary significantly in different organs. In order to identify DNA elements controlling ALDH-3 expression, we have cloned and analyzed approximately 5.5 kb of the 5' flanking region of the ALDH-3 gene. Deletion analysis showed that the 5' flanking region contains at least three functional domains: a strong promoter proximal to the transcription start site, inhibitory regions upstream of the promoter, and TCDD-responsive enhancers. The TCDD-responsive enhancers in the ALDH-3 gene were functionally similar to xenobiotic responsive elements in the cytochrome P450IA1 gene. These results indicate that transcription of the ALDH-3 gene is controlled by cooperation of at least three functional domains.
McArdle Laboratory for Cancer Research, Medical School, University of Wisconsin, Madison 53706.
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Takimoto
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Lindahl
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Dunn
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D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004252:DNA Mutational Analysis; D004742:Enhancer Elements, Genetic / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D008969:Molecular Sequence Data; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D000072317:Polychlorinated Dibenzodioxins; D011993:Recombinant Fusion Proteins; D000444:Aldehyde Dehydrogenase; D015500:Chloramphenicol O-Acetyltransferase