Carrier J S, Turgeon D, Journault K, Hum D W, Bélanger A
Oncology and Molecular Endocrinology Research Center, CHUL Research Center, Quebec, Canada.
Biochem Biophys Res Commun. 2000 Jun 7;272(2):616-21. doi: 10.1006/bbrc.2000.2795.
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.
葡糖醛酸化是药物及众多内源性化合物（如胆汁酸和甾体激素）代谢的主要途径。负责这种结合反应的酶是尿苷二磷酸葡糖醛酸基转移酶（UGT）。在UGT2B亚家族中，UGT2B7是一种存在于肝脏和多个甾体靶组织中的UGT酶，是一个重要成员，因为它能结合多种化合物，包括雌激素、雄激素、吗啡、齐多夫定和视黄酸。尽管对这种酶已有充分的表征，但编码UGT2B7蛋白的基因及其启动子区域仍不清楚。在本文中，我们报告了人类UGT2B7基因的基因组结构和启动子区域。为了分离该基因，用全长UGT2B7探针筛选了一个P1人工染色体（PAC）文库，分离出一个长度约为100 kb的克隆。除了UGT2B7基因外，这个PAC还包含另外两个先前已表征的UGT2B基因，即UGT2B26P和UGT2B27P。UGT2B7基因由六个外显子组成，跨度约16 kb，内含子范围为0.7至4.2 kb。人类UGT2B7基因的5'侧翼区域包含几个潜在的顺式作用元件，如Oct-1、Pbx-1和C/EBP。相对于起始ATG密码子的腺嘌呤碱基，在前500个核苷酸内仅在核苷酸-106处发现一个TATA盒。UGT2B7基因的表征为深入了解这个重要代谢基因的结构和调控提供了线索。
