PMID- 31653482 OWN - NLM STAT- MEDLINE DCOM- 20200122 LR - 20200122 IS - 1097-4180 (Electronic) IS - 1074-7613 (Linking) VI - 51 IP - 5 DP - 2019 Nov 19 TI - Genome-wide Analyses of Chromatin State in Human Mast Cells Reveal Molecular Drivers and Mediators of Allergic and Inflammatory Diseases. PG - 949-965.e6 LID - S1074-7613(19)30417-0 [pii] LID - 10.1016/j.immuni.2019.09.021 [doi] AB - 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 (FcepsilonRI) resulted in genome-wide reorganization of the chromatin landscape and was associated with a specific chromatin signature, which we term Ca(2+)-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 single-nucleotide 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. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Cildir, Gokhan AU - Cildir G AD - Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia; Laboratory of NF-kappaB Signaling, Institute of Molecular and Cell Biology (IMCB), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore. FAU - Toubia, John AU - Toubia J AD - Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia; ACRF Cancer Genomics Facility, Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia. FAU - Yip, Kwok Ho AU - Yip KH AD - Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia. FAU - Zhou, Mingyan AU - Zhou M AD - Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia. FAU - Pant, Harshita AU - Pant H AD - School of Medicine, University of Adelaide, Adelaide, SA, Australia. FAU - Hissaria, Pravin AU - Hissaria P AD - Royal Adelaide Hospital, Adelaide, SA 5000, Australia. FAU - Zhang, Jingxian AU - Zhang J AD - Institute of Molecular and Cell Biology (IMCB), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore. FAU - Hong, Wanjin AU - Hong W AD - Institute of Molecular and Cell Biology (IMCB), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore. FAU - Robinson, Nirmal AU - Robinson N AD - Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia. FAU - Grimbaldeston, Michele A AU - Grimbaldeston MA AD - OMNI-Biomarker Development, Genentech Inc, South San Francisco, CA 94080, USA. FAU - Lopez, Angel F AU - Lopez AF AD - Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia. FAU - Tergaonkar, Vinay AU - Tergaonkar V AD - Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia; Laboratory of NF-kappaB Signaling, Institute of Molecular and Cell Biology (IMCB), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore; Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore. Electronic address: vinayt@imcb.a-star.edu.sg. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191022 PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (Biomarkers) RN - 0 (Chromatin) RN - 0 (FGL2 protein, human) RN - 0 (Histones) RN - 37341-29-0 (Immunoglobulin E) RN - 9001-32-5 (Fibrinogen) SB - IM MH - Biomarkers MH - Cells, Cultured MH - Chromatin/*genetics/metabolism MH - Chromatin Assembly and Disassembly MH - *Disease Susceptibility MH - Fibrinogen/genetics/metabolism MH - Gene Expression Profiling MH - *Genome-Wide Association Study MH - *Genomics/methods MH - Histones/metabolism MH - Humans MH - Hypersensitivity/etiology/metabolism MH - Immunoglobulin E/immunology MH - Inflammation/etiology/metabolism MH - Mast Cells/*immunology/*metabolism MH - Polymorphism, Single Nucleotide OTO - NOTNLM OT - COC domains OT - SNPs OT - broad H3K4me3 domains OT - enhancers OT - human mast cells EDAT- 2019/10/28 06:00 MHDA- 2020/01/23 06:00 CRDT- 2019/10/27 06:00 PHST- 2018/02/28 00:00 [received] PHST- 2019/02/18 00:00 [revised] PHST- 2019/09/25 00:00 [accepted] PHST- 2019/10/28 06:00 [pubmed] PHST- 2020/01/23 06:00 [medline] PHST- 2019/10/27 06:00 [entrez] AID - S1074-7613(19)30417-0 [pii] AID - 10.1016/j.immuni.2019.09.021 [doi] PST - ppublish SO - Immunity. 2019 Nov 19;51(5):949-965.e6. doi: 10.1016/j.immuni.2019.09.021. Epub 2019 Oct 22.