First Author | Grandy R | Year | 2011 |
Journal | Mol Cell Biol | Volume | 31 |
Issue | 14 | Pages | 2997-3008 |
PubMed ID | 21606199 | Mgi Jnum | J:174075 |
Mgi Id | MGI:5051861 | Doi | 10.1128/MCB.05096-11 |
Citation | Grandy R, et al. (2011) The Ric-8B Gene Is Highly Expressed in Proliferating Preosteoblastic Cells and Downregulated during Osteoblast Differentiation in a SWI/SNF- and C/EBP{beta}-Mediated Manner. Mol Cell Biol 31(14):2997-3008 |
abstractText | The Ric-8 gene encodes a guanine exchange factor (GEF) that modulates G protein-mediated signaling, exhibiting a relevant role during regulation of cell division. In mammals, two Ric-8 homologues have been reported (Ric-8A and Ric-8B), and recent studies indicate equivalent roles for each protein. Here, we show that the Ric-8B gene is negatively regulated during osteoblast differentiation by the transcription factor C/EBPbeta. Only the larger C/EBPbeta isoform (C/EBPbeta-LAP*) downregulates Ric-8B gene promoter activity in osteoblastic cells. Accordingly, knockdown of C/EBPbeta expression by small intefering RNA in osteoblastic cells results in a significant increase of Ric-8B gene expression. Transient overexpression of Brg1 or Brm, the catalytic subunits of the SWI/SNF chromatin-remodeling complex, inhibits Ric-8B promoter activity. Also, the presence of inactive SWI/SNF complexes in osteoblastic cells results in increased endogenous Ric-8B transcription, indicating that SWI/SNF activity negatively regulates Ric-8B expression. During osteoblast differentiation, Ric-8B gene repression is accompanied by changes in nucleosome placement at the proximal Ric-8B gene promoter and reduced accessibility to regulatory sequences. |