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.
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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. :