Isolation and characterization of the human UGT2B7 gene.
Glucuronidation is a major pathway involved in the metabolism of drugs and numerous endogenous compounds, such as bile acids and steroid hormones. The enzymes responsible for this conjugation reaction are UDP-glucuronosyltransferases (UGT). Among the UGT2B subfamily, UGT2B7, a UGT enzyme present in the liver and several steroid target tissues, is an important member since it conjugates a large variety of compounds including estrogens, androgens, morphine, AZT, and retinoic acid. Although this enzyme is well characterized, the gene encoding the UGT2B7 protein and its promoter region remain unknown. In this article, we report the genomic organization and the promoter region of the human UGT2B7 gene. To isolate this gene, a P-1 artificial chromosome (PAC) library was screened with a full length UGT2B7 probe and a clone of approximately 100 kb in length was isolated. In addition to the UGT2B7 gene, this PAC contains two other UGT2B genes previously characterized, namely UGT2B26P and UGT2B27P. The UGT2B7 gene is composed of six exons spanning approximately 16 kb, with introns ranging from 0.7 to 4.2 kb. The 5'-flanking region of the human UGT2B7 gene contains several potential cis-acting elements such as Oct-1, Pbx-1, and C/EBP. Only one TATA-box at nucleotide -106 was found within the first 500 nucleotides relative to the adenine base of the initiator ATG codon. Characterization of the UGT2B7 gene provides insight into the organization and regulation of this important metabolic gene.
Carrier
J S
JS
Oncology and Molecular Endocrinology Research Center, CHUL Research Center, Quebec, Canada.
Turgeon
D
D
Journault
K
K
Hum
D W
DW
Bélanger
A
A
D001483:Base Sequence; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics; D005091:Exons / Q000235:genetics*; D020869:Gene Expression Profiling; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011544:Pseudogenes / Q000235:genetics; D020218:Response Elements / Q000235:genetics; D016385:TATA Box / Q000235:genetics
C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase