Otterness D M, Her C, Aksoy S, Kimura S, Wieben E D, Weinshilboum R M
Department of Pharmacology, Mayo Medical School/Mayo Clinic/Mayo Foundation, Rochester, MN 55905, USA.
DNA Cell Biol. 1995 Apr;14(4):331-41. doi: 10.1089/dna.1995.14.331.
Dehydroepiandrosterone sulfotransferase (DHEA ST) catalyzes the sulfate conjugation of DHEA and other steroids. From 20 to 25% of subjects are included in a subgroup with high levels of hepatic DHEA ST activity, raising the possibility that this enzyme activity might be controlled by a genetic polymorphism. To understand the molecular mechanisms involved in regulating levels of DHEA ST activity in human tissue, we cloned the human DHEA ST gene, STD. STD spans at least 17 kb and is composed of 6 exons and 5 introns. The locations of the splice junctions for several of the introns are identical to those present in the rat phenol or aryl ST gene, the only other cytosolic ST gene for which the entire exon/intron structure has been reported, as well as those present in two partially characterized genes for the rat senescence marker protein, genes that are also thought to encode ST enzymes. The 5'-flanking region of the human STD gene does not contain canonical TATA or CCAAT elements, but this region is capable of promoting transcription of a reporter gene in Hep G2 cells. Molecular cloning and structural characterization of the human STD gene will make it possible to study genetic mechanisms involved in the regulation of DHEA ST activity in human tissue.
硫酸脱氢表雄酮硫酸转移酶（DHEA ST）催化DHEA和其他类固醇的硫酸结合反应。20%至25%的受试者属于肝DHEA ST活性水平较高的亚组，这增加了该酶活性可能受基因多态性控制的可能性。为了解调控人体组织中DHEA ST活性水平所涉及的分子机制，我们克隆了人类DHEA ST基因，即STD。STD跨度至少17 kb，由6个外显子和5个内含子组成。几个内含子的剪接位点位置与大鼠酚或芳基ST基因（唯一已报道其完整外显子/内含子结构的其他胞质ST基因）以及大鼠衰老标记蛋白的两个部分特征化基因（也被认为编码ST酶的基因）中的相同。人类STD基因的5'侧翼区域不包含典型的TATA或CCAAT元件，但该区域能够促进报告基因在Hep G2细胞中的转录。人类STD基因的分子克隆和结构表征将使研究人体组织中DHEA ST活性调控所涉及的遗传机制成为可能。
