Genome-wide Analyses of Chromatin State in Human Mast Cells Reveal Molecular Drivers and Mediators of Allergic and Inflammatory Diseases

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Genome-wide Analyses of Chromatin State in Human Mast Cells Reveal Molecular Drivers and Mediators of Allergic and Inflammatory Diseases
Title:
Genome-wide Analyses of Chromatin State in Human Mast Cells Reveal Molecular Drivers and Mediators of Allergic and Inflammatory Diseases
Journal Title:
Immunity
Publication Date:
22 October 2019
Citation:
Cildir, G., Toubia, J., Yip, K. H., Zhou, M., Pant, H., Hissaria, P., … Tergaonkar, V. (2019). Genome-wide Analyses of Chromatin State in Human Mast Cells Reveal Molecular Drivers and Mediators of Allergic and Inflammatory Diseases. Immunity, 51(5), 949–965.e6. doi:10.1016/j.immuni.2019.09.021
Abstract:
Mast cells (MCs) are versatile immune cells capable of rapidly responding to a diverse range of extracellular cues. Here, we mapped the genomic and transcriptomic changes in human MCs upon diverse stimuli. Our analyses revealed broad H3K4me3 domains and enhancers associated with activation. Notably, the rise of intracellular calcium concentration upon immunoglobulin E (IgE)-mediated crosslinking of the high-affinity IgE receptor (FcεRI) resulted in genome-wide reorganization of the chromatin landscape and was associated with a specific chromatin signature, which we term Ca2+- dependent open chromatin (COC) domains. Examination of differentially expressed genes revealed potential effectors of MC function, and we provide evidence for fibrinogen-like protein 2 (FGL2) as an MC mediator with potential relevance in chronic spontaneous urticaria. Disease-associated singlenucleotide polymorphisms mapped onto cis-regulatory regions of human MCs suggest that MC function may impact a broad range of pathologies. The datasets presented here constitute a resource for the further study of MC function.
License type:
Publisher Copyright
Funding Info:
This research / project is supported by the National Research Foundation - Competitive Research Programme
Grant Reference no. : NRF-CRP17- 2017-02

National Health and Medical Research Council (NHMRC) of Australia through program grant 105253 and project grant 1127290; and the Premier’s Research and Industry Fund grant provided by the South Australian Government Department of State Development

This research is supported by core funding from: Institute of Molecular and Cell Biology
Grant Reference no. :
Description:
ISSN:
1074-7613