High-affinity binding sites to the vitamin D receptor DNA binding domain in the human growth hormone promoter

High-affinity binding sites to the vitamin D receptor DNA binding domain in the human growth hormone promoter
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DOI:
10.1006/bbrc.1998.8884
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发表时间:
1998-06-29
影响因子:
3.1
通讯作者:
Perez-Fernandez, R
Perez-Fernandez, R
中科院分区:
生物学4区
文献类型:
--
作者:
Alonso, M;Segura, C;Perez-Fernandez, R

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1,25(OH)(2)D-3对人生长激素(HGH)基因的调控是一个知之甚少的机制。本研究的目的是研究hGH基因是否具有维生素D受体DNA结合域的DNA识别元件。利用凝胶滞留分析和足迹技术,在hGH的5‘-侧翼序列中鉴定出两个高亲和力结合位点,命名为F1和F2。远端序列F1位于-59个碱基上,由一个由3个碱基隔开的不完全的直接重复序列组成,与其他已知的维生素D反应元件(VDRE)具有高度的相似性。F2位于-36个碱基上,显示了单一的7个碱基的序列,这与其他已知的VDRE不同。这两个位点的位置(F1靠近GHF-1/Pit-1反应元件,F2接触TATA盒)表明维生素D受体本身或通过干扰其他转录因子可能调节hGH的表达。(C)1998年学术出版社。
The regulation of the human growth hormone (hGH) gene by 1,25(OH)(2)D-3 is a mechanism which is poorly understood. The objective of this study was to investigate whether the hGH gene has DNA recognition elements for the DNA binding domain of the vitamin D receptor. Using gel retardation assays and footprinting techniques, two high-affinity binding sites, denominated F1 and F2, were identified in the 5'-flanking sequence of hGH. The distal site, F1, located at -59 bp is made up of an imperfect direct repeat separated by 3 bp and showed a high degree of similarity with other known vitamin D response elements (VDREs). The proximal site, F2, located at -36 bp showed a single 7-bp sequence, which is different from other known VDREs. The location of both sites (F1 near the GHF-1/Pit-1 response element, F2 contacting the TATA box) suggests that the vitamin D receptor by itself or through interference with other transcriptional factors may modulate hGH expression. (C) 1998 Academic Press.