Phosphorylation-mediated control of chromatin organization and transcriptional activity of the tissue-specific osteocalcin gene
UMass Chan Affiliations
Department of Cell Biology and Cancer CenterGraduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
1999-02-18Keywords
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 DLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
J Cell Biochem. 1999 Mar 15;72(4):586-94.
DOI
10.1002/(SICI)1097-4644(19990315)72:4<586::AID-JCB13>3.0.CO;2-KPermanent Link to this Item
http://hdl.handle.net/20.500.14038/34222PubMed ID
10022617Related Resources
ae974a485f413a2113503eed53cd6c53
10.1002/(SICI)1097-4644(19990315)72:4<586::AID-JCB13>3.0.CO;2-K