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.
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoblastos
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Fatores de Transcrição
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Transcrição Gênica
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Proteínas Nucleares
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Proteínas Cromossômicas não Histona
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Fatores de Troca do Nucleotídeo Guanina
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Proteína beta Intensificadora de Ligação a CCAAT
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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