Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment.
Nat Immunol
; 17(8): 956-65, 2016 08.
Article
in 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Repressor Proteins
/
T-Lymphocytes
/
Gene Expression Regulation, Developmental
/
Tumor Suppressor Proteins
/
Lymphopoiesis
/
GATA3 Transcription Factor
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Hepatocyte Nuclear Factor 1-alpha
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Receptors, Notch
/
Core Binding Factor Alpha 2 Subunit
Limits:
Animals
Language:
En
Journal:
Nat Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2016
Document type:
Article
Affiliation country:
United States