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

Toxicol Appl Pharmacol. 2001 Jul 1;174(1):60-8. doi: 10.1006/taap.2001.9191.


UDP-glucuronosyltransferase 1A6 (UGT1A6), a key enzyme catalyzing the glucuronidation 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5' Untranslated Regions
  • Animals
  • Base Sequence
  • Benzo(a)pyrene / pharmacology
  • DNA, Complementary / chemistry
  • Digestive System / enzymology
  • Exons
  • Gene Expression*
  • Glucuronosyltransferase / genetics*
  • Humans
  • Kidney / enzymology
  • Liver / enzymology
  • Male
  • Methylcholanthrene / pharmacology
  • Molecular Sequence Data
  • Promoter Regions, Genetic*
  • Pyrazines / pharmacology
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment
  • Thiones
  • Thiophenes
  • beta-Naphthoflavone / pharmacology


  • 5' Untranslated Regions
  • DNA, Complementary
  • Pyrazines
  • RNA, Messenger
  • Thiones
  • Thiophenes
  • Benzo(a)pyrene
  • Methylcholanthrene
  • beta-Naphthoflavone
  • oltipraz
  • Glucuronosyltransferase