Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require CCAAT/enhancer-binding protein beta-dependent recruitment of SWI/SNF activity.
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.
Villagra
Alejandro
A
Departamento de Bioquimica y Biologia Molecular, Facultad de Ciencias Biologicas, Universidad de Concepcion, Casilla 160-C, 4079100 Concepcion, Chile.
Cruzat
Fernando
F
Carvallo
Loreto
L
Paredes
Roberto
R
Olate
Juan
J
van Wijnen
Andre J
AJ
Stein
Gary S
GS
Lian
Jane B
JB
Stein
Janet L
JL
Imbalzano
Anthony N
AN
Montecino
Martin
M
D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D020134:Catalytic Domain; D002762:Cholecalciferol / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D005786:Gene Expression Regulation; D008954:Models, Biological; D008957:Models, Genetic; D010006:Osteoblasts / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D014158:Transcription, Genetic
D022782:CCAAT-Enhancer-Binding Protein-beta; D002843:Chromatin; D015675:Osteocalcin; D002762:Cholecalciferol