Kahlen J P, Carlberg C
Clinique de Dermatologie, Hôpital Cantonal Universitaire, Genève, Switzerland.
Biochem Biophys Res Commun. 1996 Jan 26;218(3):882-6. doi: 10.1006/bbrc.1996.0157.
The classical action of the hormone 1,25-dihydroxyvitamin D3 (VD) is the regulation of calcium metabolism. In contrast, the peptide hormone atrial natriuretic factor (ANF) is one of the few known nonclassical VD responding genes. We screened the promoter of the rat ANF gene and identified a typical VD receptor (VDR) binding site formed by a direct repeat of two hexameric core binding motifs spaced by three nucleotides, between positions -907 and -891. Like most of the DR3-type VD response elements this sequence is bound with high affinity (Kd = 0.53 nM) by a heterodimer formed by VDR and retinoid X receptor. In a heterologous promoter context one copy of this sequence mediated an about fourfold gene activation by VD and a half-maximal activation (EC50) value of 0.48 nM VD. This characterizes the identified sequence as one of the most potent VD response elements.
激素1,25 - 二羟基维生素D3（VD）的经典作用是调节钙代谢。相比之下，肽激素心钠素（ANF）是少数已知的非经典VD反应基因之一。我们筛选了大鼠ANF基因的启动子，并在-907至-891位之间鉴定出一个典型的VD受体（VDR）结合位点，该位点由两个六聚体核心结合基序直接重复形成，中间间隔三个核苷酸。与大多数DR3型VD反应元件一样，该序列被VDR和视黄酸X受体形成的异源二聚体以高亲和力（Kd = 0.53 nM）结合。在异源启动子背景下，该序列的一个拷贝介导了VD约四倍的基因激活，VD的半最大激活（EC50）值为0.48 nM。这表明所鉴定的序列是最有效的VD反应元件之一。
