Intrinsically disordered domain of transcription factor TCF-1 is required for T cell developmental fidelity.
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
11
10
2022
accepted:
20
07
2023
medline:
23
10
2023
pubmed:
18
8
2023
entrez:
17
8
2023
Statut:
ppublish
Résumé
In development, pioneer transcription factors access silent chromatin to reveal lineage-specific gene programs. The structured DNA-binding domains of pioneer factors have been well characterized, but whether and how intrinsically disordered regions affect chromatin and control cell fate is unclear. Here, we report that deletion of an intrinsically disordered region of the pioneer factor TCF-1 (termed L1) leads to an early developmental block in T cells. The few T cells that develop from progenitors expressing TCF-1 lacking L1 exhibit lineage infidelity distinct from the lineage diversion of TCF-1-deficient cells. Mechanistically, L1 is required for activation of T cell genes and repression of GATA2-driven genes, normally reserved to the mast cell and dendritic cell lineages. Underlying this lineage diversion, L1 mediates binding of TCF-1 to its earliest target genes, which are subject to repression as T cells develop. These data suggest that the intrinsically disordered N terminus of TCF-1 maintains T cell lineage fidelity.
Identifiants
pubmed: 37592014
doi: 10.1038/s41590-023-01599-7
pii: 10.1038/s41590-023-01599-7
doi:
Substances chimiques
Transcription Factors
0
T Cell Transcription Factor 1
0
Chromatin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1698-1710Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL145754
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016520
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA248041
Pays : United States
Organisme : NIAID NIH HHS
ID : F30 AI161873
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK112217
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK112217
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA230800
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI091627
Pays : United States
Organisme : NIAID NIH HHS
ID : F30 AI174776
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA052715
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK127768
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI168240
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI168136
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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