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Inducible chromatin priming is associated with the establishment of immunological memory in T cells

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Bevington, S. L., Cauchy, P., Piper, Jason, Bertrand, E., Lalli, N, Jarvis, R. C., Gilding, L. N., Ott, Sascha, Bonifer, C. and Cockerill, P. N. (2016) Inducible chromatin priming is associated with the establishment of immunological memory in T cells. The EMBO Journal, 35 (5). pp. 515-535. doi:10.15252/embj.201592534

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Official URL: http://dx.doi.org/10.15252/embj.201592534

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Abstract

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.

Item Type: Journal Article
Subjects: Q Science > QR Microbiology > QR180 Immunology
Divisions: Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre
Library of Congress Subject Headings (LCSH): Immunity, Chromatin, Epigenetics, T cells , Genetic regulation
Journal or Publication Title: The EMBO Journal
Publisher: Nature Publishing Group
ISSN: 0261-4189
Official Date: 1 March 2016
Dates:
DateEvent
1 March 2016Published
21 January 2016Available
22 December 2015Accepted
Volume: 35
Number: 5
Page Range: pp. 515-535
DOI: 10.15252/embj.201592534
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
UNSPECIFIEDBiotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
UNSPECIFIEDBloodwisehttp://dx.doi.org/10.13039/501100007903

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