Cited by 226Genomics and Chromatin DynamicsT-cell and B-cell ImmunologyDevelopmental Biology and Gene Regulation

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Lineage-Determining Transcription Factor TCF-1 Initiates the Epigenetic Identity of T Cells

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Johnson, John L., Georgakilas, Georgios, Petrovic, Jelena, Kurachi, Makoto, Cai, Stanley, Harly, Christelle, Pear, Warren S., Bhandoola, Avinash, Wherry, E. John, Vahedi, Golnaz·2018·Immunity

DOI 10.1016/j.immuni.2018.01.012PMC PMC5824646

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Abstract

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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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: Johnson, John L.
Georgakilas, Georgios
Petrovic, Jelena
Kurachi, Makoto
Harly, Christelle
Pear, Warren S.
Bhandoola, Avinash
Wherry, E. John
Vahedi, Golnaz
Venue: Immunity
Publisher: Elsevier BV
Published: 2018-02
Volume: 48
Issue: 2
Pages: 243-257.e10
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2018.01.012
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 384 d)
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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Lineage-Determining Transcription Factor TCF-1 Initiates the Epigenetic Identity of T Cells

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