B cell-specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers.
Nat Immunol
; 11(2): 148-54, 2010 Feb.
Article
en En
| MEDLINE
| ID: mdl-19966806
ABSTRACT
Activation-induced cytidine deaminase (AID) is essential for the generation of antibody memory but also targets oncogenes, among other genes. We investigated the transcriptional regulation of Aicda (which encodes AID) in class switch-inducible CH12F3-2 cells and found that Aicda regulation involved derepression by several layers of positive regulatory elements in addition to the 5' promoter region. The 5' upstream region contained functional motifs for the response to signaling by cytokines, the ligand for the costimulatory molecule CD40 or stimuli that activated the transcription factor NF-kappaB. The first intron contained functional binding elements for the ubiquitous silencers c-Myb and E2f and for the B cell-specific activator Pax5 and E-box-binding proteins. Our results show that Aicda is regulated by the balance between B cell-specific and stimulation-responsive elements and ubiquitous silencers.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Genes de Inmunoglobulinas
/
Linfocitos B
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Regulación de la Expresión Génica
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Elementos de Facilitación Genéticos
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Citidina Desaminasa
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Elementos Silenciadores Transcripcionales
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Japón