Abstract
We have analyzed the linkage of protein phosphorylation to the remodeling of chromatin structure that accompanies transcriptional activity of the rat osteocalcin (OC) gene in bone-derived cells. Short incubations with okadaic acid, an inhibitor of protein phosphatases 1 and 2A, induced marked changes in the chromatin organization of the OC gene promoter. These changes were reflected by loss of the two DNase I hypersensitive sites normally present in bone-derived cells expressing this gene. These hypersensitive sites include the elements that control basal tissue-specific expression, as well as steroid hormone regulation. Indeed, the absence of hypersensitivity was accompanied by inhibition of basal and vitamin D- dependent enhancement of OC gene transcription. The effects of okadaic acid on OC chromatin structure and gene activity were specific and reversible. Staurosporine, a protein kinase C inhibitor, did not significantly affect transcriptional activity or DNase I hypersensitivity of the OC gene. We conclude that cellular phosphorylation-dephosphorylation events distinct from protein kinase C-dependent reactions are required for both chromatin remodeling and transcriptional activity of the OC gene in osseous cells.
Original language | English (US) |
---|---|
Pages (from-to) | 586-594 |
Number of pages | 9 |
Journal | Journal of cellular biochemistry |
Volume | 72 |
Issue number | 4 |
DOIs | |
State | Published - Mar 15 1999 |
Keywords
- Chromatin structure
- Okadaic acid
- Osteocalcin gene
- Transcriptional regulation
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology