多个启动子指导新型N端变体人维生素D受体基因转录本的组织特异性表达。
Multiple promoters direct the tissue-specific expression of novel N-terminal variant human vitamin D receptor gene transcripts.
作者信息
Crofts L A, Hancock M S, Morrison N A, Eisman J A
机构信息
Bone and Mineral Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
出版信息
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10529-34. doi: 10.1073/pnas.95.18.10529.
Abstract
The effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] are mediated by the vitamin D receptor (VDR), a member of the nuclear receptor superfamily of transcriptional regulators. We have identified upstream exons of the human (h) VDR gene that are incorporated into variant transcripts, two of which encode N-terminal variant receptor proteins. Expression of the hVDR gene, which spans more than 60 kb and consists of at least 14 exons, is directed by two distinct promoters. A tissue-specific distal promoter generates unique transcripts in tissues involved in calcium regulation by 1, 25-(OH)2D3 and can direct the expression of a luciferase reporter gene in a cell line-specific manner. These major N-terminal differences in hVDR transcripts, potentially resulting in structural differences in the expressed receptor, may contribute to cellular responsiveness to 1,25-(OH)2D3 through tissue differences in the regulation of VDR expression.
摘要
1,25 - 二羟基维生素D3 [1,25-(OH)2D3] 的作用是由维生素D受体（VDR）介导的，VDR是转录调节因子核受体超家族的成员。我们已经鉴定出人类（h）VDR基因的上游外显子，它们被纳入可变转录本中，其中两个编码N端可变受体蛋白。hVDR基因跨度超过60 kb，由至少14个外显子组成，其表达由两个不同的启动子指导。一个组织特异性的远端启动子在参与1,25-(OH)2D3钙调节的组织中产生独特的转录本，并能以细胞系特异性的方式指导荧光素酶报告基因的表达。hVDR转录本中这些主要的N端差异可能导致所表达受体的结构差异，可能通过VDR表达调节的组织差异来影响细胞对1,25-(OH)2D3的反应性。
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