title: 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.
abstract: 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/EBPβ. Only the larger C/EBPβ isoform (C/EBPβ-LAP*) downregulates Ric-8B gene promoter activity in osteoblastic cells. Accordingly, knockdown of C/EBPβ 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.
authors: Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, and FONDAP Center forGenome Regulation, Universidad Andres Bello, Santiago, Chile.
authors: Rodrigo
authors: R
authors: Grandy
authors: Hugo
authors: H
authors: Sepulveda
authors: Rodrigo
authors: R
authors: Aguilar
authors: Philippe
authors: P
authors: Pihan
authors: Berta
authors: B
authors: Henriquez
authors: Juan
authors: J
authors: Olate
authors: Martin
authors: M
authors: Montecino
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