An alternative promoter contributes to tissue- and inducer-specific expression of the rat UDP-glucuronosyltransferase 1A6 gene

被引:24
作者
Auyeung, DJ [1 ]
Kessler, FK [1 ]
Ritter, JK [1 ]
机构
[1] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA
关键词
UDP-glucuronosyltransferase; benzo[alpha]pyrene; gene regulation; alternative promoter; hepatic nuclear factor;
D O I
10.1006/taap.2001.9191
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
UDP-glucuronosyltransferase 1A6 (UGT1A6), a key enzyme catalyzing the glucuropidation of small planar phenols and amines, is expressed in a tissue- and inducer-dependent manner. Expression is high in kidney, gastrointestinal tract, and induced liver, with low expression in spleen, lung, and ovary. Exposure to certain chemicals, such as 3-methylcholanthrene, benzo[a]pyrene, beta -naphthoflavone, and oltipraz elevates UGT1A6 mRNA in liver and to a lesser extent gastrointestinal tract and kidney, but not in other tissues. The mechanisms underlying this complex pattern of expression have been elusive. We have identified a new type of UGT1A6 mRNA (class 2) that differs in its 5' untranslated sequence. The class 2 transcript is the more abundant type expressed in liver, gastrointestinal tract, and kidney. Transcription of the class 2 mRNA is initiated 107 bases 5' of the UGT1A6 coding exon. The promoter region flanking the transcription start site contains an HNF1-like binding site identical to that in the human UGT1A6 gene. Both class 1 and class 2 mRNAs were elevated in liver by 3-methylcholanthrene, benzo[a]pyrene, beta -naphthoflavone, and oltipraz, with preferential elevation of class 1 occurring after 3-methylcholanthrene and benzo[a]pyrene treatment. These data suggest that transcription from a second promoter contributes to tissue- and inducer-specific expression of rat UGT1A6. (C) 2001 Academic Press.
引用
收藏
页码:60 / 68
页数:9
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