Zierold C, Darwish H M, DeLuca H F
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison 53706.
Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):900-2. doi: 10.1073/pnas.91.3.900.
The calcidiol (25-hydroxyvitamin D3) 24-hydroxylase is one of the key enzymes in the metabolism of vitamin D. This enzyme acts on both calcidiol and calcitriol (1,25-dihydroxyvitamin D3) to initiate degradation of these potent vitamin D metabolites and is tightly regulated. Calcitriol itself induces this enzyme and acts at the transcriptional level. Transcriptional regulation of genes by calcitriol has been shown to occur via the vitamin D-receptor binding to a vitamin D-response element located upstream of the transcription start site. We now report a vitamin D-response element located between nt -262 and nt -238 of the rat calcidiol 24-hydroxylase gene. This sequence binds the calcitriol receptor and confers vitamin D-dependent transactivation of transcription to its own, as well as heterologous, promoter.
骨化二醇(25-羟基维生素D3)24-羟化酶是维生素D代谢的关键酶之一。该酶作用于骨化二醇和骨化三醇(1,25-二羟基维生素D3),启动这些强效维生素D代谢产物的降解,且受到严格调控。骨化三醇自身可诱导该酶,并在转录水平发挥作用。已证明骨化三醇对基因的转录调控是通过维生素D受体与位于转录起始位点上游的维生素D反应元件结合来实现的。我们现在报告在大鼠骨化二醇24-羟化酶基因的nt -262至nt -238之间存在一个维生素D反应元件。该序列可结合骨化三醇受体,并赋予其自身以及异源启动子维生素D依赖性的转录反式激活作用。