Landscape of stimulation-responsive chromatin across diverse human immune cells
Landscape of stimulation-responsive chromatin across diverse human immune cells
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DOI：
10.1038/s41588-019-0505-9
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发表时间：
2019-10-01
期刊：
影响因子：
30.8
通讯作者：
Pritchard, Jonathan K.
中科院分区：
文献类型：
--
作者：
Calderon, Diego;Nguyen, Michelle L. T.;Pritchard, Jonathan K.
免疫系统的一个标志是在静息状态和刺激状态之间过渡的专门细胞类型之间的相互作用。这种动态系统的基因调控景观尚未在人类细胞中得到充分表征。在这里，我们收集了多达32个免疫细胞群体在静息和刺激条件下使用测序（ATAC-seq）和RNA测序数据的转座酶可接近染色质的测定。刺激引起广泛的染色质重塑，包括受刺激的B和T细胞之间共享的反应元件。此外，一些自身免疫性状在来自不同细胞类型的刺激响应元件中显示出显著的遗传性，突出了这些细胞状态在自身免疫中的重要性。等位基因特异性读段作图鉴定了在特定条件下改变染色质可及性的变体，使我们能够观察到候选因果变体的功能证据，该候选因果变体在静息细胞中的现有大规模研究中未检测到。我们的研究结果提供了一个染色质动力学的资源，并强调需要表征刺激细胞中遗传变异的影响。
A hallmark of the immune system is the interplay among specialized cell types transitioning between resting and stimulated states. The gene regulatory landscape of this dynamic system has not been fully characterized in human cells. Here we collected assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing data under resting and stimulated conditions for up to 32 immune cell populations. Stimulation caused widespread chromatin remodeling, including response elements shared between stimulated B and T cells. Furthermore, several autoimmune traits showed significant heritability in stimulation-responsive elements from distinct cell types, highlighting the importance of these cell states in autoimmunity. Allele-specific read mapping identified variants that alter chromatin accessibility in particular conditions, allowing us to observe evidence of function for a candidate causal variant that is undetected by existing large-scale studies in resting cells. Our results provide a resource of chromatin dynamics and highlight the need to characterize the effects of genetic variation in stimulated cells.