Dataset Information

Intrinsically disordered domain of transcription factor TCF-1 is required for T cell developmental fidelity

ABSTRACT: 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 low-complexity intrinsically disordered regions (IDRs) affect chromatin and control cell fate is unclear. Here, we report deletion of an IDR 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 de-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 TCF-1’s intrinsically disordered N-terminus maintains T cell lineage fidelity.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Simone Sidoli

LAB HEAD: Simone Sidoli

PROVIDER: PXD043586 | Pride | 2024-06-16

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	20230219_Simone_Naomi_Delta-L1_1.raw	Raw
	20230219_Simone_Naomi_Delta-L1_2.raw	Raw
	20230219_Simone_Naomi_Delta-L1_3.raw	Raw
	20230219_Simone_Naomi_Delta_L1_input_1.msf	Msf
	20230219_Simone_Naomi_Delta_L1_input_1.raw	Raw

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Publications

Intrinsically disordered domain of transcription factor TCF-1 is required for T cell developmental fidelity.

Goldman Naomi N Chandra Aditi A Johnson Isabelle I Sullivan Matthew A MA Patil Abhijeet R AR Vanderbeck Ashley A Jay Atishay A Zhou Yeqiao Y Ferrari Emily K EK Mayne Leland L Aguilan Jennifer J Xue Hai-Hui HH Faryabi Robert B RB John Wherry E E Sidoli Simone S Maillard Ivan I Vahedi Golnaz G

Nature immunology 20230817 10

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 progenit ...[more]

PMID: 37592014

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