Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D3.

SA Kerner, RA Scott, JW Pike - Proceedings of the National …, 1989 - National Acad Sciences
SA Kerner, RA Scott, JW Pike
Proceedings of the National Academy of Sciences, 1989National Acad Sciences
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 …
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.
National Acad Sciences