Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require CCAAT/enhancer-binding protein β-dependent recruitment of SWI/SNF activity

Alejandro Villagra, Fernando Cruzat, Loreto Carvallo, Roberto Paredes, Juan Olate, Andre J. Van Wijnen, Gary S. Stein, Jane B. Lian, Janet L. Stein, Anthony N. Imbalzano, Martin Montecino

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63 Scopus citations

Abstract

Tissue-specific activation of the osteocalcin (OC) gene is associated with changes in chromatin structure at the promoter region. Two nuclease- hypersensitive sites span the key regulatory elements that control basal tissue-specific and vitamin D3-enhanced OC gene transcription. To gain understanding of the molecular mechanisms involved in chromatin remodeling of the OC gene, we have examined the requirement for SWI/SNF activity. We inducibly expressed an ATPase-defective BRG1 catalytic subunit that forms inactive SWI/SNF complexes that bind to the OC promoter. This interaction results in inhibition of both basal and vitamin D3-enhanced OC gene transcription and a marked decrease in nuclease hypersensitivity. We find that SWI/SNF is recruited to the OC promoter via the transcription factor CCAAT/enhancer-binding protein β, which together with Runx2 forms a stable complex to facilitate RNA polymerase II binding and activation of OC gene transcription. Together, our results indicate that the SWI/SNF complex is a key regulator of the chromatin-remodeling events that promote tissue-specific transcription in osteoblasts.

Original languageEnglish (US)
Pages (from-to)22695-22706
Number of pages12
JournalJournal of Biological Chemistry
Volume281
Issue number32
DOIs
Publication statusPublished - Aug 11 2006

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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