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A functional N-terminal domain in C/EBPß-LAP* is required for interacting with SWI/SNF and to repress Ric-8B gene transcription in osteoblasts.
Aguilar, Rodrigo; Grandy, Rodrigo; Meza, Daniel; Sepulveda, Hugo; Pihan, Philippe; van Wijnen, Andre J; Lian, Jane B; Stein, Gary S; Stein, Janet L; Montecino, Martin.
Afiliação
  • Aguilar R; Center for Biomedical Research and FONDAP Center for Genome Regulation, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago, Chile.
J Cell Physiol ; 229(10): 1521-8, 2014 Oct.
Article em En | MEDLINE | ID: mdl-24585571
The chromatin remodeling complex SWI/SNF and the transcription factor C/EBPß play critical roles in osteoblastic cells as they jointly control transcription of a number of bone-related target genes. The largest C/EBPß isoform, LAP*, possesses a short additional N-terminal domain that has been proposed to mediate the interaction of this factor with SWI/SNF in myeloid cells. Here we examine the requirement of a functional N-terminus in C/EBPß-LAP* for binding SWI/SNF and for recruiting this complex to the Ric-8B gene to mediate transcriptional repression. We find that both C/EBPß-LAP* and SWI/SNF simultaneously bind to the Ric-8B promoter in differentiating osteoblasts that repress Ric-8B expression. This decreased expression of Ric-8B is not accompanied by significant changes in histone acetylation at the Ric-8B gene promoter sequence. A single aminoacid change at the C/EBPß-LAP* N-terminus (R3L) that inhibits C/EBPß-LAP*-SWI/SNF interaction, also prevents SWI/SNF recruitment to the Ric-8B promoter as well as C/EBPß-LAP*-dependent repression of the Ric-8B gene. Inducible expression of the C/EBPß-LAP*R3L protein in stably transfected osteoblastic cells demonstrates that this mutant protein binds to C/EBPß-LAP*-target promoters and competes with the endogenous C/EBPß factor. Together our results indicate that a functional N-terminus in C/EBPß-LAP* is required for interacting with SWI/SNF and for Ric-8B gene repression in osteoblasts.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoblastos / Fatores de Transcrição / Transcrição Gênica / Proteínas Nucleares / Proteínas Cromossômicas não Histona / Fatores de Troca do Nucleotídeo Guanina / Proteína beta Intensificadora de Ligação a CCAAT / Montagem e Desmontagem da Cromatina Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Cell Physiol Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Chile País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoblastos / Fatores de Transcrição / Transcrição Gênica / Proteínas Nucleares / Proteínas Cromossômicas não Histona / Fatores de Troca do Nucleotídeo Guanina / Proteína beta Intensificadora de Ligação a CCAAT / Montagem e Desmontagem da Cromatina Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Cell Physiol Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Chile País de publicação: Estados Unidos