Multiple promoters direct the tissue-specific expression of novel N-terminal variant human vitamin D receptor gene transcripts

The effects of 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] 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)(2)D(3) 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)(2)D(3) through tissue differences in the regulation of VDR expression.

1,25-二羟基维生素D₃[1,25-(OH)₂D₃]的生物学效应由维生素D受体（VDR, vitamin D receptor）介导，该受体属于转录调节因子核受体超家族成员。本研究鉴定出人类（h）VDR基因的上游外显子，这些外显子可整合进入可变转录本，其中两种转录本能够编码N端变异的受体蛋白。人类VDR基因全长跨越超过60 kb，至少包含14个外显子，其转录表达由两个不同的启动子驱动。其中一种组织特异性远端启动子可在参与1,25-(OH)₂D₃介导的钙调节过程的组织中产生特异性转录本，且能够以细胞系特异性的方式介导荧光素酶报告基因的表达。人类VDR转录本存在上述主要的N端差异，这可能会导致表达的受体蛋白产生结构差异，或可通过VDR表达调控的组织特异性差异，影响细胞对1,25-(OH)₂D₃的应答反应。