Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment.
Nat Immunol
; 17(8): 956-65, 2016 08.
Article
em 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
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Linfócitos T
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Regulação da Expressão Gênica no Desenvolvimento
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Proteínas Supressoras de Tumor
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Linfopoese
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Fator de Transcrição GATA3
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Fator 1-alfa Nuclear de Hepatócito
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Receptores Notch
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Subunidade alfa 2 de Fator de Ligação ao Core
Limite:
Animals
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos