Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require C/EBPbeta -dependent recruitment of SWI/SNF activity

doi:10.1074/jbc.M511640200

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Papers In Press, published online ahead of print June 13, 2006
J. Biol. Chem, 10.1074/jbc.M511640200
Submitted on October 27, 2005
Accepted on June 12, 2006

Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require C/EBP $beta$ -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, and Martin Montecino

BIochemistry and Molecular Biology, University of Concepcion, Concepcion 4079100

Corresponding Author: mmonteci{at}udec.cl

Tissue-specific activation of the osteocalcin (OC) gene is associated with changes in chromatin structure at the promoter region. Two nuclease hypersentive 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 which 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 C/EBP $beta$ which together with Runx2 forms a stable complex to facilitate RNA pol 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.

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Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require C/EBP-dependent recruitment of SWI/SNF activity

Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require C/EBP $beta$ -dependent recruitment of SWI/SNF activity