澳大利亚南澳大学Vinay Tergaonkar小组的一项最新研究，通过分析人肥大细胞（MC）中染色质状态的全基因组揭示了过敏性和炎性疾病的分子驱动因素和介导因子。这一研究成果发表在11月19日出版的国际学术期刊《免疫》上。

研究人员绘制了人类MC在不同刺激下的基因组和转录组变化。研究人员的分析揭示了广泛的H3K4me3域和与激活相关的增强子。值得注意的是，在免疫球蛋白E（IgE）介导的高亲和力IgE受体（FcεRI）交联后，细胞内钙浓度的升高导致了染色质景观的全基因组重组，并与特定的染色质特征相关，这被称之为Ca²⁺依赖性开放染色质（COC）域。

差异表达基因的检查揭示了MC功能的潜在效应，研究人员为纤维蛋白原样蛋白2（FGL2）作为与慢性自发性荨麻疹的潜在相关性的MC介导因子提供了证据。映射到人类MC的顺式调控区域的与疾病相关的单核苷酸多态性表明，MC功能可能影响广泛的病理学。这些数据集构成了进一步研究MC功能的资源。

据了解，MC是一种多功能免疫细胞，能够快速响应多种细胞外信号。

附：英文原文

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

Author: Gkhan Cildir, John Toubia, Kwok Ho Yip, Mingyan Zhou, Harshita Pant, Pravin Hissaria, Jingxian Zhang, Wanjin Hong, Nirmal Robinson, Michele A. Grimbaldeston, Angel F. Lopez, Vinay Tergaonkar

Issue&Volume: 2019/11/19

Abstract: Mast cells (MCs) are versatile immune cells capable of rapidly responding to a diverserange of extracellular cues. Here, we mapped the genomic and transcriptomic changesin human MCs upon diverse stimuli. Our analyses revealed broad H3K4me3 domains andenhancers associated with activation. Notably, the rise of intracellular calcium concentrationupon immunoglobulin E (IgE)-mediated crosslinking of the high-affinity IgE receptor(FcεRI) resulted in genome-wide reorganization of the chromatin landscape and wasassociated with a specific chromatin signature, which we term Ca2+-dependent open chromatin (COC) domains. Examination of differentially expressed genesrevealed potential effectors of MC function, and we provide evidence for fibrinogen-likeprotein 2 (FGL2) as an MC mediator with potential relevance in chronic spontaneousurticaria. Disease-associated single-nucleotide polymorphisms mapped onto cis-regulatory regions of human MCs suggest that MC function may impact a broad rangeof pathologies. The datasets presented here constitute a resource for the furtherstudy of MC function.

DOI: 10.1016/j.immuni.2019.09.021

Source: https://www.cell.com/immunity/fulltext/S1074-7613(19)30417-0