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The Transcription Factor Runx3 Establishes Chromatin Accessibility of cis-Regulatory Landscapes that Drive Memory Cytotoxic T Lymphocyte Formation
Open accessAbstract
T cell receptor (TCR) stimulation of naive CD8+ T cells initiates reprogramming of cis-regulatory landscapes that specify effector and memory cytotoxic T lymphocyte (CTL) differentiation. We mapped regions of hyper-accessible chromatin in naive cells during TCR stimulation and discovered that the transcription factor (TF) Runx3 promoted accessibility to memory CTL-specific cis-regulatory regions before the first cell division and was essential for memory CTL differentiation. Runx3 was specifically required for accessibility to regions highly enriched with IRF, bZIP and Prdm1-like TF motifs, upregulation of TFs Irf4 and Blimp1, and activation of fundamental CTL attributes in early effector and memory precursor cells. Runx3 ensured that nascent CTLs differentiated into memory CTLs by preventing high expression of the TF T-bet, slowing effector cell proliferation, and repressing terminal CTL differentiation. Runx3 overexpression enhanced memory CTL differentiation during iterative infections. Thus, Runx3 governs chromatin accessibility during TCR stimulation and enforces the memory CTL developmental program.
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“Additionally, T RM cells can be identified by the upregulation of specific transcription factors such as HOBIT (homolog of Blimp-1 in T cells), RUNX3 (runt-related transcription factor 3), and BLIMP-1 (B lymphocyte-induced maturation protein-1), which lead to transcriptional reprogramming to downregulate tissue egress genes and upregulate tissue retention markers. 295-298”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [297]
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Metadata
- Authors
- Wang, D., Diao, H., Getzler, A. J., Rogal, W., Frederick, M. A., Milner, J., Yu, B., Crotty, S., Goldrath, A. W., & Pipkin, M. E.
- Affiliations
- Scripps Research Institute (US)
- University of California San Diego (US)
- La Jolla Institute for Immunology (US)
- Corresponding author
- Pipkin, Matthew E.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 48
- Issue
- 4
- Pages
- 659-674.e6
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC6750808
- OpenAlex
- W2800450153
- Cited by
- 201
- References
- 55
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 19 · 2023: 31 · 2022: 29 · 2021: 32 · 2020: 27 · 2019: 12 · 2018: 6
- FWCI
- 9.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01 AI095634, NIH U19 AI109976)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- RUNX3, chromatin accessibility, cis-regulatory elements, T cell differentiation, T cell receptor stimulation, naive T cells, IRF4, Blimp-1, T-bet, effector T cells, transcription factor binding motifs, terminal differentiation
- MeSH terms
- Positive Regulatory Domain I-Binding Factor 1, Interferon Regulatory Factor-4, Animals, Binding Sites, Cell Differentiation, Cell Line, Chlorocebus aethiops, Chromatin, Enzyme Activation, Female, Cricetinae, Humans, Immunologic Memory, Male, Mice, Inbred C57BL, Receptors, Antigen, T-Cell, T-Lymphocytes, Cytotoxic, Vero Cells, Mice, Knockout, Cell Proliferation, Core Binding Factor Alpha 3 Subunit, Interferon Regulatory Factors, Mice
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