Inducible chromatin priming is associated with the establishment of immunological memory in T cells
Open accessAbstract
Immunological memory is a defining feature of vertebrate physiology, allowing rapid responses to repeat infections. However, the molecular mechanisms required for its establishment and maintenance remain poorly understood. Here, we demonstrated that the first steps in the acquisition of T‐cell memory occurred during the initial activation phase of naïve T cells by an antigenic stimulus. This event initiated extensive chromatin remodeling that reprogrammed immune response genes toward a stably maintained primed state, prior to terminal differentiation. Activation induced the transcription factors NFAT and AP‐1 which created thousands of new DNase I‐hypersensitive sites (DHSs), enabling ETS‐1 and RUNX1 recruitment to previously inaccessible sites. Significantly, these DHSs remained stable long after activation ceased, were preserved following replication, and were maintained in memory‐phenotype cells. We show that primed DHSs maintain regions of active chromatin in the vicinity of inducible genes and enhancers that regulate immune responses. We suggest that this priming mechanism may contribute to immunological memory in T cells by facilitating the induction of nearby inducible regulatory elements in previously activated T cells.
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The study sheds light on previously described immune-related transcriptional programs where assisted loading was not suggested but seems plausible in light of our findings.
“Our study also sheds light on previously described immune-related transcriptional programs where assisted loading was not suggested but seems plausible in light of our findings24, 56, 57.”
From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [24]
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- Authors
- Bevington, S. L., Cauchy, P., Piper, J., Bertrand, E., Lalli, N., Jarvis, R. C., Gilding, L. N., Ott, S., Bonifer, C., & Cockerill, P. N.
- Affiliations
- University of Birmingham (GB)
- University of Warwick (GB)
- University of Leeds (GB)
- Corresponding author
- Cockerill, Peter N
- ORCID
- Venue
- The EMBO Journal
- Published
- 2016-01-21
- Volume
- 35
- Issue
- 5
- Pages
- 515-535
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC4772849
- OpenAlex
- W2314739834
- Cited by
- 110
- References
- 4
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 3 · 2023: 9 · 2022: 15 · 2021: 13 · 2020: 10 · 2019: 10 · 2018: 8 · 2017: 15 · 2016: 10
- FWCI
- 7.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The EMBO Journal (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Warwick Research Archive Portal (University of Warwick) (acceptedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- Funders
- BBSRC
- Bloodwise
- 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 › Signaling Pathways in Disease
- Keywords
- immunological memory, T cell memory, chromatin remodeling, DNase I hypersensitive sites, naive T cell activation, NFAT, AP-1, ETS1, RUNX1, enhancers, transcriptional reprogramming
- MeSH terms
- Animals, Cells, Cultured, Chromatin, Deoxyribonuclease I, Humans, Immunologic Memory, Interleukin-3, Mice, Transgenic, RNA, Messenger, Spleen, T-Lymphocytes, Gene Expression, Granulocyte-Macrophage Colony-Stimulating Factor, Transcription Factor AP-1, Jurkat Cells, Core Binding Factor Alpha 2 Subunit, NFATC Transcription Factors, Proto-Oncogene Protein c-ets-1, Chemokine CCL1
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