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)2D3 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.
Alonso
M
M
Department of Physiology, School of Medicine, University of Santiago de Compostela, Spain.
Segura
C
C
Dieguez
C
C
Perez-Fernandez
R
R
D001665:Binding Sites / Q000235:genetics; D002117:Calcitriol / Q000502:physiology; D018983:DNA Footprinting; D015342:DNA Probes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D013006:Growth Hormone / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000737:chemistry*; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics; D014809:Vitamin D-Binding Protein / Q000235:genetics
D015342:DNA Probes; D004268:DNA-Binding Proteins; C494187:POU1F1 protein, human; D018167:Receptors, Calcitriol; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D014809:Vitamin D-Binding Protein; D013006:Growth Hormone; D002117:Calcitriol