Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment.
Nat Immunol
; 17(8): 956-65, 2016 08.
Article
en En
| MEDLINE
| ID: mdl-27376470
ABSTRACT
During T cell development, multipotent progenitors relinquish competence for other fates and commit to the T cell lineage by turning on Bcl11b, which encodes a transcription factor. To clarify lineage commitment mechanisms, we followed developing T cells at the single-cell level using Bcl11b knock-in fluorescent reporter mice. Notch signaling and Notch-activated transcription factors collaborate to activate Bcl11b expression irrespectively of Notch-dependent proliferation. These inputs work via three distinct, asynchronous mechanisms an early locus 'poising' function dependent on TCF-1 and GATA-3, a stochastic-permissivity function dependent on Notch signaling, and a separate amplitude-control function dependent on Runx1, a factor already present in multipotent progenitors. Despite their necessity for Bcl11b expression, these inputs act in a stage-specific manner, providing a multitiered mechanism for developmental gene regulation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Linfocitos T
/
Regulación del Desarrollo de la Expresión Génica
/
Proteínas Supresoras de Tumor
/
Linfopoyesis
/
Factor de Transcripción GATA3
/
Factor Nuclear 1-alfa del Hepatocito
/
Receptores Notch
/
Subunidad alfa 2 del Factor de Unión al Sitio Principal
Límite:
Animals
Idioma:
En
Revista:
Nat Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos