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Intriniscally disordered domain of transcription factor TCF-1 is requried for T cell developmental fidelity [CUT&RUN]

ABSTRACT: Intriniscally disordered domain of transcription factor TCF-1 is requried for T cell developmental fidelity [CUT&RUN]

PROVIDER: PRJNA991516 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25143872_1.fastq.gz	Fastqsanger.gz
	SRR25143872_2.fastq.gz	Fastqsanger.gz
	SRR25143873_1.fastq.gz	Fastqsanger.gz
	SRR25143873_2.fastq.gz	Fastqsanger.gz
	SRR25143874_1.fastq.gz	Fastqsanger.gz

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Intriniscally disordered domain of transcription factor TCF-1 is requried for T cell developmental fidelity [CUT&RUN]

Project description:The transcription factor TCF-1 has long been demonstrated to be essential for normal T cell development, with a critical role at the earliest stages of lineage specification downstream of Notch signaling in the thymus. Recent work has shown that TCF-1 targets and is essential for the opening of chromatin in T cells to orchestrate the gene regulatory cascade that occurs during development. However, besides the high mobility group DNA binding domain, no portion of the TCF-1 protein has been characterized to determine its role in hematopoiesis. In this study, we fully characterize all regions of TCF-1 and assess their importance in TCF-1-driven epigenetic and transcriptional regulation as well as in endowing developmental competency to the T cell lineage. Surprisingly, we identified an intrinsically disordered N-terminal region of TCF-1 termed “L1” that is necessary for efficient transition from early thymic progenitors to double-negative (DN)2 T cells. The few T cells that develop from progenitor cells expressing mutant TCF-1 lacking the L1 region exhibit lineage infidelity that was distinct and unique from the lineage diversion of TCF-1-deficient cells. Transcriptional and epigenetic profiling indicated that the L1 region was required for efficient target gene transactivation which correlated with the de-repression of a set of Gata2-driven genes normally restricted to the mast cell and dendritic cell lineages. DL1 mutant DN2 cells showed aberrant opening of previously silent chromatin at mast cell genes and Gata2-bound enhancers. These data support an essential role for TCF-1’s intrinsically disordered N-terminus in maintaining fidelity to the T cell lineage through carefully balanced activation of partner transcription factors that are required to repress alternative lineages.

2023-07-06 | GSE236516 | GEO

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

Project description: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.

2024-06-16 | PXD043586 | Pride

Intriniscally disordered domain of transcription factor TCF-1 is requried for T cell developmental fidelity [RNA-Seq]

2023-07-06 | GSE213236 | GEO

Intriniscally disordered domain of transcription factor TCF-1 is requried for T cell developmental fidelity [ATAC-Seq]

2023-07-06 | GSE213234 | GEO

Intriniscally disordered domain of transcription factor TCF-1 is requried for T cell developmental fidelity

Project description:Intriniscally disordered domain of transcription factor TCF-1 is requried for T cell developmental fidelity

| PRJNA880016 | ENA

Intriniscally disordered domain of transcription factor TCF-1 is requried for T cell developmental fidelity [RNA-Seq]

Project description:Intriniscally disordered domain of transcription factor TCF-1 is requried for T cell developmental fidelity [RNA-Seq]

| PRJNA880026 | ENA

Intriniscally disordered domain of transcription factor TCF-1 is requried for T cell developmental fidelity [ATAC-Seq]

Project description:Intriniscally disordered domain of transcription factor TCF-1 is requried for T cell developmental fidelity [ATAC-Seq]

| PRJNA880022 | ENA

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

Project description: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.

| S-EPMC10919931 | biostudies-literature

Multiple regulatory intrinsically disordered motifs control FOXO4 transcription factor binding and function

Project description:Transcription factors harbour defined intrinsically disordered regulatory regions, which raises the question of how they mediate binding to structured co-regulators and how this regulates activity. Here, we present a detailed molecular regulatory mechanism of Forkhead box O4 (FOXO4) by the structured transcriptional co-regulator β-catenin. We find that the largely disordered FOXO4 C-terminal region, which contains its transactivation domain binds β-catenin through two defined interaction sites, and this is regulated by combined PKB/AKT- and CK1-mediated phosphorylation. Binding of β-catenin competes with the auto-inhibitory interaction of the FOXO4 disordered region with its DNA-binding forkhead domain, and thereby enhances FOXO4 transcriptional activity. Furthermore, we show that binding of the β-catenin inhibitor protein ICAT is compatible with FOXO4 binding to β-catenin, suggesting that ICAT acts as a molecular switch between anti-proliferative FOXO and pro-proliferative Wnt/TCF/LEF signalling. Together these data illustrate how the interplay of intrinsically disordered regions, post-translational modifications and co-factor binding contribute to transcription factor function. Highlights • The interaction network between FOXO4 and β-catenin was deciphered • FOXO4 auto-inhibition interferes with DNA binding and is counter-acted by β-catenin • FOXO4 exists in multiple conformations regulated by phosphorylation and co-factors • ICAT switches between FOXO4 and TCF/LEF transcription factors

2022-04-15 | PXD026263 | Pride

Intriniscally disordered domain of transcription factor TCF-1 is requried for T cell developmental fidelity

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-07-06 | GSE213238 | GEO