Cited by 205Genomics and Chromatin DynamicsT-cell and B-cell ImmunologyDevelopmental Biology and Gene Regulation

The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.

Transformation of Accessible Chromatin and 3D Nucleome Underlies Lineage Commitment of Early T Cells

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Abstract

How chromatin reorganization coordinates differentiation and lineage commitment from hematopoietic stem and progenitor cells (HSPCs) to mature immune cells has not been well understood. Here, we carried out an integrative analysis of chromatin accessibility, topologically associating domains, AB compartments, and gene expression from HSPCs to CD4+CD8+ T cells. We found that abrupt genome-wide changes at all three levels of chromatin organization occur during the transition from double-negative stage 2 (DN2) to DN3, accompanying the T lineage commitment. The transcription factor BCL11B, a critical regulator of T cell commitment, is associated with increased chromatin interaction, and Bcl11b deletion compromised chromatin interaction at its target genes. We propose that these large-scale and concerted changes in chromatin organization present an energy barrier to prevent the cell from reversing its fate to earlier stages or redirecting to alternatives and thus lock the cell fate into the T lineages.

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Crossref · 10.1016/j.immuni.2018.01.013

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Metadata

Authors
Hu, G., Cui, K., Fang, D., Hirose, S., Wang, X., Wangsa, D., Jin, W., Ried, T., Liu, P., Zhu, J., Rothenberg, E. V., & Zhao, K.
Affiliations
  • National Institutes of Health (US)
  • California Institute of Technology (US)
  • Wellcome Sanger Institute (GB)
Corresponding author
  • Hu, Gangqing
  • Rothenberg, Ellen V.
  • Zhao, Keji
Venue
Immunity
Publisher
Elsevier BV
Published
2018-02
Volume
48
Issue
2
Pages
227-242.e8
ISSN
1074-7613 (ISSN-L)
OpenAlex
W2788037203
Cited by
199
References
70
Citations by year
2026: 5 · 2025: 11 · 2024: 15 · 2023: 40 · 2022: 33 · 2021: 34 · 2020: 24 · 2019: 27 · 2018: 10
FWCI
8.45
Type
journal article
Language
en
Open access
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Funders
  • Division of Intramural Research of the National Cancer Institute
  • National Institute of Allergy and Infectious Diseases
  • NHLBI
  • NIH (R01 AI083514)
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
T cell lineage commitment, chromatin accessibility, 3D genome organization, topologically associating domains, A/B compartments, hematopoietic stem and progenitor cells, double-negative T cells, BCL11B, chromatin interactions, cell fate determination, T cell differentiation
MeSH terms
Animals, Cell Differentiation, Cell Nucleus, Chromatin, Humans, Repressor Proteins, T-Lymphocytes, Cell Lineage, Tumor Suppressor Proteins

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