A novel RBP-J kappa-dependent switch from C/EBP beta to C/EBP zeta at the C/EBP binding site on the C-reactive protein promoter.
J Immunol
; 178(11): 7302-9, 2007 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-17513780
ABSTRACT
Regulation of basal and cytokine (IL-6 and IL-1beta)-induced expression of C-reactive protein (CRP) in human hepatoma Hep3B cells occurs during transcription. A critical transcriptional regulatory element on the CRP promoter is a C/EBP binding site overlapping a NF-kappaB p50 binding site. In response to IL-6, C/EBPbeta and p50 occupy the C/EBP-p50 site on the CRP promoter. The aim of this study was to identify the transcription factors occupying the C/EBP-p50 site in the absence of C/EBPbeta. Accordingly, we treated Hep3B nuclear extract with a C/EBP-binding consensus oligonucleotide to generate an extract lacking active C/EBPbeta. Such treated nuclei contain only C/EBPzeta (also known as CHOP10 and GADD153) because the C/EBP-binding consensus oligonucleotide binds to all C/EBP family proteins except C/EBPzeta. EMSA using this extract revealed formation of a C/EBPzeta-containing complex at the C/EBP-p50 site on the CRP promoter. This complex also contained RBP-Jkappa, a transcription factor known to interact with kappaB sites. RBP-Jkappa was required for the formation of C/EBPzeta-containing complex. The RBP-Jkappa-dependent C/EBPzeta-containing complexes were formed at the C/EBP-p50 site on the CRP promoter in the nuclei of primary human hepatocytes also. In luciferase transactivation assays, overexpressed C/EBPzeta abolished both C/EBPbeta-induced and (IL-6 + IL-1beta)-induced CRP promoter-driven luciferase expression. These results indicate that under basal conditions, C/EBPzeta occupies the C/EBP site, an action that requires RBP-Jkappa. Under induced conditions, C/EBPzeta is replaced by C/EBPbeta and p50. We conclude that the switch between C/EBPbeta and C/EBPzeta participates in regulating CRP transcription. This process uses a novel phenomenon, that is, the incorporation of RBP-Jkappa into C/EBPzeta complexes solely to support the binding of C/EBPzeta to the C/EBP site.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteína C-Reactiva
/
Región de Cambio de la Inmunoglobulina
/
Regiones Promotoras Genéticas
/
Proteínas Potenciadoras de Unión a CCAAT
/
Proteína beta Potenciadora de Unión a CCAAT
/
Factor de Transcripción CHOP
/
Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos