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Publication : The Ric-8B gene is highly expressed in proliferating preosteoblastic cells and downregulated during osteoblast differentiation in a SWI/SNF- and C/EBPbeta-mediated manner.

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.
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