Title

Phosphorylation-mediated control of chromatin organization and transcriptional activity of the tissue-specific osteocalcin gene

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology and Cancer Center

Date

2-18-1999

Document Type

Article

Medical Subject Headings

Animals; Chromatin; Deoxyribonuclease I; Enzyme Inhibitors; Gene Expression Regulation; Okadaic Acid; Osteocalcin; Phosphoprotein Phosphatases; Phosphorylation; Promoter Regions (Genetics); Protein Kinase C; Rats; Staurosporine; Tumor Cells, Cultured; Vitamin D

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: J Cell Biochem. 1999 Mar 15;72(4):586-94.

Related Resources

Link to article in PubMed