Phosphorylation-mediated control of chromatin organization and transcriptional activity of the tissue-specific osteocalcin gene
Graduate School of Biomedical Sciences; Department of Cell Biology and Cancer Center
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
Life Sciences | Medicine and Health Sciences
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.
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Citation: J Cell Biochem. 1999 Mar 15;72(4):586-94.