Transcriptional regulation of the rat NAD(P)H:quinone reductase gene. Identification of regulatory elements controlling basal level expression and inducible expression by planar aromatic compounds and phenolic antioxidants.
We have identified two regions in the 5'-flanking sequence of the rat quinone reductase gene that contain xenobiotic responsive elements. The DNA sequence of the first region spans nucleotides -393 to -352 of the 5'-flanking region and shares sequence identity with the xenobiotic responsive element (XRE) described for the cytochrome P-450 CYPIA1 gene. The DNA sequence of the second region spans nucleotides -434 to -404 of the 5'-flanking region of the quinone reductase structural gene. When a synthetic oligonucleotide corresponding to nucleotides -434 to -404 was inserted in front of a heterologous promoter linked to the chloramphenicol acetyltransferase structural gene, an increase in basal level expression as well as responsiveness to beta-naphthoflavone and t-butylhydroquinone, but not 2,3,7,8-tetrachlorodibenzo-p-dioxin, was observed. The sequence, -434 to -404, did not have any sequence identity with the XRE but shared a large degree of identity with the antioxidant responsive element recently described for the rat glutathione S-transferase Ya subunit gene (Rushmore, T. H., King, R. G., Paulson, K. E., and Pickett, C. B. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 3826-3830; Rushmore, T. H., and Pickett, C. B. (1990) J. Biol. Chem. 265, 14648-14653). These results indicate that the antioxidant responsive element can be distinguished functionally from the classical XRE and is also involved in the regulation of the quinone reductase gene by planar aromatic compounds and phenolic antioxidants.
Favreau
L V
LV
Merck Frosst Centre for Therapeutic Research, Pointe-Claire-Dorval, Quebec, Canada.
Pickett
C B
CB
D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic; D005982:Glutathione Transferase / Q000235:genetics; D008969:Molecular Sequence Data; D016660:NAD(P)H Dehydrogenase (Quinone); D009841:Oligonucleotides / Q000737:chemistry; D010636:Phenols / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011808:Quinone Reductases / Q000235:genetics*; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic; D015262:Xenobiotics / Q000494:pharmacology*
D000975:Antioxidants; D009841:Oligonucleotides; D010636:Phenols; D015262:Xenobiotics; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D005982:Glutathione Transferase