HIGH-AFFINITY BINDING-SITES TO THE VITAMIN-D-RECEPTOR DNA-BINDING DOMAIN IN THE HUMAN GROWTH-HORMONE PROMOTER

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 stu dy was to investigate whether the hGH gene has DNA recognition element s for the DNA binding domain of the vitamin D receptor. Using gel reta rdation assays and footprinting techniques, two high-affinity binding sites, denominated F1 and F2, were identified in the 5'-flanking seque nce of hGH. The distal site, F1, located at -59 bp is made up of an im perfect direct repeat separated by 3 bp and showed a high degree of si milarity with other known vitamin D response elements (VDREs). The pro ximal 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 n ear the GHF-1/Pit-1 response element, F2 contacting the TATA box) sugg ests that the vitamin D receptor by itself or through interference wit h other transcriptional factors may modulate hGH expression. (C) 1998 Academic Press.