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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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
StatePublished - Aug 11 2006
Externally publishedYes

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CCAAT-Enhancer-Binding Proteins
Chromatin Assembly and Disassembly
Osteocalcin
Chromatin
Bone
Genes
Bone and Bones
Transcription
Cholecalciferol
Tissue
Transcriptional Activation
Chemical activation
RNA Polymerase II
Osteoblasts
Genetic Promoter Regions
Adenosine Triphosphatases
Catalytic Domain
Hypersensitivity
Transcription Factors

ASJC Scopus subject areas

  • Biochemistry

Cite this

Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require CCAAT/enhancer-binding protein β-dependent recruitment of SWI/SNF activity. / Villagra, Alejandro; Cruzat, Fernando; Carvallo, Loreto; Paredes, Roberto; Olate, Juan; Van Wijnen, Andre J.; Stein, Gary S.; Lian, Jane B.; Stein, Janet L.; Imbalzano, Anthony N.; Montecino, Martin.

In: Journal of Biological Chemistry, Vol. 281, No. 32, 11.08.2006, p. 22695-22706.

Research output: Contribution to journalArticle

Villagra, A, Cruzat, F, Carvallo, L, Paredes, R, Olate, J, Van Wijnen, AJ, Stein, GS, Lian, JB, Stein, JL, Imbalzano, AN & Montecino, M 2006, 'Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require CCAAT/enhancer-binding protein β-dependent recruitment of SWI/SNF activity', Journal of Biological Chemistry, vol. 281, no. 32, pp. 22695-22706. https://doi.org/10.1074/jbc.M511640200
Villagra, Alejandro ; Cruzat, Fernando ; Carvallo, Loreto ; Paredes, Roberto ; Olate, Juan ; Van Wijnen, Andre J. ; Stein, Gary S. ; Lian, Jane B. ; Stein, Janet L. ; Imbalzano, Anthony N. ; Montecino, Martin. / Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require CCAAT/enhancer-binding protein β-dependent recruitment of SWI/SNF activity. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 32. pp. 22695-22706.
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