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Integration of kinase and calcium signaling at the level of chromatin underlies inducible gene activation in T cells
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Brignall, Ruth, Cauchy, Pierre, Bevington, Sarah L., Gorman, Bethany, Pisco, Angela O., Bagnall, James, Boddington, Christopher, Rowe, William, England, Hazel, Rich, Kevin, Schmidt, Lorraine, Dyer, Nigel P., Travis, Mark A., Ott, Sascha, Jackson, Dean A., Cockerill, Peter N. and Paszek, Pawel (2017) Integration of kinase and calcium signaling at the level of chromatin underlies inducible gene activation in T cells. The Journal of Immunology, 199 (8). pp. 2652-2667. ji1602033. doi:10.4049/jimmunol.1602033 ISSN 0022-1767.
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Official URL: http://dx.doi.org/10.4049/jimmunol.1602033
Abstract
TCR signaling pathways cooperate to activate the inducible transcription factors NF-κB, NFAT, and AP-1. In this study, using the calcium ionophore ionomycin and/or PMA on Jurkat T cells, we show that the gene expression program associated with activation of TCR signaling is closely related to specific chromatin landscapes. We find that calcium and kinase signaling cooperate to induce chromatin remodeling at ∼2100 chromatin regions, which demonstrate enriched binding motifs for inducible factors and correlate with target gene expression. We found that these regions typically function as inducible enhancers. Many of these elements contain composite NFAT/AP-1 sites, which typically support cooperative binding, thus further reinforcing the need for cooperation between calcium and kinase signaling in the activation of genes in T cells. In contrast, treatment with PMA or ionomycin alone induces chromatin remodeling at far fewer regions (∼600 and ∼350, respectively), which mostly represent a subset of those induced by costimulation. This suggests that the integration of TCR signaling largely occurs at the level of chromatin, which we propose plays a crucial role in regulating T cell activation.
Item Type: | Journal Article | ||||||||||||||||||
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Subjects: | Q Science > QR Microbiology | ||||||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Science > Computer Science Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre |
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Library of Congress Subject Headings (LCSH): | T cells -- Genetic aspects, Chromatin | ||||||||||||||||||
Journal or Publication Title: | The Journal of Immunology | ||||||||||||||||||
Publisher: | American Association of Immunologists | ||||||||||||||||||
ISSN: | 0022-1767 | ||||||||||||||||||
Official Date: | 15 October 2017 | ||||||||||||||||||
Dates: |
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Volume: | 199 | ||||||||||||||||||
Number: | 8 | ||||||||||||||||||
Page Range: | pp. 2652-2667 | ||||||||||||||||||
Article Number: | ji1602033 | ||||||||||||||||||
DOI: | 10.4049/jimmunol.1602033 | ||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||
Date of first compliant deposit: | 11 January 2018 | ||||||||||||||||||
Date of first compliant Open Access: | 11 January 2018 | ||||||||||||||||||
Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Wellcome Trust (London, England), Seventh Framework Programme (European Commission) (FP7) | ||||||||||||||||||
Grant number: | BB/K003097/1, BB/ I017976/1 (BBSRC), 097820/Z/11/B, 203128/Z/16/Z (Wellcome Trust (London, England)), Grant 305564 (FP7) | ||||||||||||||||||
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