Title
Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require CCAAT/enhancer-binding protein beta-dependent recruitment of SWI/SNF activity
UMMS Affiliation
Graduate School of Biomedical Sciences; Departamento de Bioquimica y Biologia Molecular; Department of Cell Biology
Date
6-15-2006
Document Type
Article
Medical Subject Headings
Animals; CCAAT-Enhancer-Binding Protein-beta; Catalytic Domain; Cholecalciferol; Chromatin; *Gene Expression Regulation; Models, Biological; Models, Genetic; Osteoblasts; Osteocalcin; Promoter Regions (Genetics); Rats; Transcription, Genetic
Disciplines
Life Sciences | Medicine and Health Sciences
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 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.
Rights and Permissions
Citation: J Biol Chem. 2006 Aug 11;281(32):22695-706. Epub 2006 Jun 13. Link to article on publisher's site