The vitamin D-responsive element in the human osteocalcin gene. Association with a nuclear proto-oncogene enhancer.
A vitamin D-responsive element (VDRE) locus within the 5' region of the human osteocalcin gene promoter contains a steroid response-like half-site immediately proximal to a consensus site for the AP-1 nuclear oncogene family. In the studies described here, internal mutagenesis of the osteocalcin promoter coupled to functional assays reveal that the interaction of the vitamin D receptor is limited to the proximal region of the VDRE locus. Mutations within the distal AP-1 consensus site reduce the basal activity of the promoter but have little effect on vitamin D inducibility. The absolute level of promoter activity induced by hormone, however, is dramatically reduced in the absence of an intact AP-1 site suggesting a functional synergism between the receptor and AP-1-related proteins. In vitro receptor-DNA binding studies confirm the lack of requirement for the distal component in receptor binding. These results suggest that the osteocalcin VDRE is limited to 15 nucleotides closely juxtaposed to a distal functional AP-1 site. The close association of the two sites may lead to proto-oncogene and steroid receptor interactions that result in interesting functional consequences.
Ozono
K
K
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
Liao
J
J
Kerner
S A
SA
Scott
R A
RA
Pike
J W
JW
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004742:Enhancer Elements, Genetic; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000737:chemistry; D015675:Osteocalcin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D051381:Rats; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D014807:Vitamin D / Q000502:physiology*
C000715470:MAS1 protein, human; D009841:Oligonucleotides; D000090063:Proto-Oncogene Mas; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D015675:Osteocalcin; D014807:Vitamin D