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

Martin Montecino, André J. Van Wijnen, Jane B. Lian, Janet L. Stein, Gary S. Stein

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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 languageEnglish (US)
Pages (from-to)586-594
Number of pages9
JournalJournal of cellular biochemistry
Volume72
Issue number4
DOIs
StatePublished - Mar 15 1999

Keywords

  • Chromatin structure
  • Okadaic acid
  • Osteocalcin gene
  • Transcriptional regulation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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