Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D3.
Osteoblast-specific expression of the bone protein osteocalcin is controlled at the transcriptional level by the steroid hormone 1 alpha,25-dihydroxyvitamin D3. As this protein may represent a marker for bone activity in human disease, we examined the regulation of its expression at the molecular level by evaluating human osteocalcin gene promoter function. We describe regions within the promoter that contribute to basal expression of the gene in osteoblast-like cells in culture. Further, we define a 21-base-pair DNA element with the sequence 5'-GTGACTCACCGGGTGAACGGG-3', which acts in cis to mediate 1 alpha,25-dihydroxyvitamin D3 inducibility of the osteocalcin gene. This response element bears sequence similarity with other short DNA segments, particularly those for estrogen and thyroid hormone, which act together with their respective trans-acting receptors to modulate gene transcription.
Kerner
S A
SA
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.
Scott
R A
RA
Pike
J W
JW
D001483:Base Sequence; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002478:Cells, Cultured / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D015675:Osteocalcin; D010957:Plasmids; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D002135:Calcium-Binding Proteins; D015675:Osteocalcin; D002117:Calcitriol