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

van Wijnen A.J.; Lian J.B.; Stein J.L.; Stein G.S.; Montecino, M.

Keywords: acid, isolation, rat, enzyme, region, animals, expression, phosphorylation, transcription, binding, regions, rats, protein, cell, gene, specificity, tumor, site, chromatin, regulation, inhibitor, tissue, inhibitors, article, kinase, promoter, phosphatase, osteocalcin, vitamin, staurosporine, condensation, controlled, phosphoprotein, animal, c, study, derivative, priority, nonhuman, journal, Cells,, Cultured, I, (Genetics), Deoxyribonuclease, okadaic, D, colecalciferol

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.

Más información

Título de la Revista: JOURNAL OF CELLULAR BIOCHEMISTRY
Volumen: 72
Número: 4
Editorial: Wiley
Fecha de publicación: 1999
Página de inicio: 586
Página final: 594
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-0033559678&partnerID=q2rCbXpz