title: Comparative studies of human UDP-glucuronosyltransferase 1A8 and 1A9 proximal promoters using single base substitutions.
abstract: The nucleotide sequences of the proximal promoters of UDP-glucuronosyltransferase (UGT) 1A8 and 1A9 genes are very similar. However, UGT1A8 and 1A9 are mainly expressed in extra-hepatic and hepatic cells, respectively. Using mutants of UGT1A8 and 1A9 proximal promoters, we revealed their critical differences in terms of promoter activity and the role of the T-repeat region (T-region) conserved in both promoters. In extra-hepatic cells, Caco2, the activity of UGT1A9 proximal promoter increased to 73.4 ± 8.5% of that of the UGT1A8 proximal promoter with only 4 base changes: -160C, -152A, -62T, and -59G. The derivatives of the T-region showed that this region is not necessary for promoter activity, but the length of T repeats influences the activity somewhat. Therefore, the cause of the low activity of the UGT1A9 proximal promoter may be not only 4 base changes, but also the truncation of T repeats. From these results, the UGT1A9 proximal promoter was assumed to change into the non-active form from the original sequence, and this might be one of the reasons for the tissue-specific expression of UGT1A9.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Qingdao University.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Xiao
authors.forename: Kana
authors.initials: K
authors.lastname: Nunome
authors.forename: Taemi
authors.initials: T
authors.lastname: Yahara
authors.forename: Emi
authors.initials: E
authors.lastname: Inoue
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nabeshima
authors.forename: Shirou
authors.initials: S
authors.lastname: Tsuchida
authors.forename: Naoya
authors.initials: N
authors.lastname: Hamaue
authors.forename: Takashi
authors.initials: T
authors.lastname: Aoki
mesh_terms: D001483:Base Sequence; D018938:Caco-2 Cells; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D000090264:UDP-Glucuronosyltransferase 1A9
chemical_list: C000715591:UGT1A9 protein, human; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9; C454320:UDP-glucuronosyltransferase, UGT1A8