Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require CCAAT/enhancer-binding protein beta-dependent recruitment of SWI/SNF activity
Graduate School of Biomedical Sciences; Departamento de Bioquimica y Biologia Molecular; Department of Cell Biology
Life Sciences | Medicine and Health Sciences
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 beta, 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.
DOI of Published Version
J Biol Chem. 2006 Aug 11;281(32):22695-706. Epub 2006 Jun 13. Link to article on publisher's site
The Journal of biological chemistry
Villagra A, Cruzat F, Carvallo L, Paredes R, Olate J, Van Wijnen AJ, Stein GS, Lian JB, Stein JL, Imbalzano AN, Montecino MA. (2006). Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require CCAAT/enhancer-binding protein beta-dependent recruitment of SWI/SNF activity. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1074/jbc.M511640200. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1316