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Lineage-Determining Transcription Factor TCF-1 Initiates the Epigenetic Identity of T Cells
Open accessAbstract
T cell development is orchestrated by transcription factors that regulate the expression of genes initially buried within inaccessible chromatin, but the transcription factors that establish the regulatory landscape of the T cell lineage remain unknown. Profiling chromatin accessibility at eight stages of T cell development revealed the selective enrichment of TCF-1 at genomic regions that became accessible at the earliest stages of development. TCF-1 was further required for the accessibility of these regulatory elements and at the single-cell level, it dictated a coordinate opening of chromatin in T cells. TCF-1 expression in fibroblasts generated de novo chromatin accessibility even at chromatin regions with repressive marks, inducing the expression of T cell-restricted genes. These results indicate that a mechanism by which TCF-1 controls T cell fate is through its widespread ability to target silent chromatin and establish the epigenetic identity of T cells.
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“PU.1 recognition motifs are the most highly enriched of all defined motifs at sites that start out highly accessible in early pro-T cell stages, when PU.1 is present, and lose accessibility during commitment, i.e., as PU.1 levels decline (44, 85, 95).”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [95]
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Metadata
- Authors
- Johnson, J. L., Georgakilas, G., Petrovic, J., Kurachi, M., Cai, S., Harly, C., Pear, W. S., Bhandoola, A., Wherry, E. J., & Vahedi, G.
- Affiliations
- University of Pennsylvania (US)
- National Institutes of Health (US)
- Corresponding author
- Vahedi, Golnaz
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 48
- Issue
- 2
- Pages
- 243-257.e10
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC5824646
- OpenAlex
- W2788726131
- Cited by
- 226
- References
- 57
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 23 · 2023: 37 · 2022: 37 · 2021: 37 · 2020: 36 · 2019: 12 · 2018: 15
- FWCI
- 8.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- National Cancer Institute (P01CA119070, R01CA215518)
- National Institute of Allergy and Infectious Diseases (R01AI115712, R01AI047833, R01AI105343, K22AI112570, U19AI117950, P01AI112521, R21AI117718, U19AI082630, P01AI108545)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- TCF1, T cell development, chromatin accessibility, transcription factors, lineage determination, chromatin opening, T cell fate
- MeSH terms
- Animals, Chromatin, Fibroblasts, T-Lymphocytes, Transcription, Genetic, Cell Lineage, NIH 3T3 Cells, Chromatin Assembly and Disassembly, Mice, Hepatocyte Nuclear Factor 1-alpha, T Cell Transcription Factor 1, Epigenomics
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