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大鼠骨化三醇24-羟化酶基因启动子中维生素D受体同二聚体型反应元件的鉴定。

Identification of a vitamin D receptor homodimer-type response element in the rat calcitriol 24-hydroxylase gene promoter.

作者信息

Kahlen J P, Carlberg C

机构信息

Clinique de Dermatologie, Hôpital Cantonal Universitaire, Genève, Switzerland.

出版信息

Biochem Biophys Res Commun. 1994 Aug 15;202(3):1366-72. doi: 10.1006/bbrc.1994.2081.

DOI:10.1006/bbrc.1994.2081
PMID:8060315
Abstract

Calcitriol (1,25-dihydroxyvitamin D3, VD) controls multiple aspects of homeostasis, cell growth and differentiation by the action of its nuclear receptor (VDR), which binds to, and activates transcription from, response elements in the promoter region of its target genes. One of these target genes is calcitriol 24-hydroxylase, an enzyme that initiates the degradation of 25-dihydroxyvitamin D3 (calcidiol) and calcitriol. We screened the promoter of rat calcitriol 24-hydroxylase for potential VDR binding sites and identified a functional VD response element, between positions -250 and -233. This response element consists of two directly repeated hexameric core binding motifs spaced by six nucleotides and confers VD-dependent transactivation mediated by VDR homodimers or alternatively by heterodimers formed by VDR and retinoic acid receptor (RAR). Its structure and function are very similar to those of the homodimer-type response element of the human osteocalcin promoter.

摘要

骨化三醇(1,25 - 二羟基维生素D3,VD)通过其核受体(VDR)的作用来控制体内平衡、细胞生长和分化的多个方面,该核受体与靶基因启动子区域的反应元件结合并激活其转录。这些靶基因之一是骨化三醇24 - 羟化酶,一种启动25 - 二羟基维生素D3(骨化二醇)和骨化三醇降解的酶。我们筛选了大鼠骨化三醇24 - 羟化酶的启动子以寻找潜在的VDR结合位点,并在-250至-233位之间鉴定出一个功能性VD反应元件。该反应元件由两个直接重复的六聚体核心结合基序组成,间隔六个核苷酸,并赋予由VDR同二聚体或由VDR和视黄酸受体(RAR)形成的异二聚体介导的VD依赖性反式激活。其结构和功能与人类骨钙素启动子的同二聚体型反应元件非常相似。

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