Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 31, Issue 14, Pages 2997-3008Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.05096-11
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Funding
- FONDECYT [1095075, 1090150, 3110138]
- FONDAP [15090007]
- CONICYT
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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/EBP beta. Only the larger C/EBP beta isoform (C/EBP beta-LAP*) downregulates Ric-8B gene promoter activity in osteoblastic cells. Accordingly, knockdown of C/EBP beta 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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