Sepsis, sequela of bloodstream infections and dysregulated host responses, is a leading cause of death globally. Neutrophils tightly regulate responses to pathogens to prevent organ damage. Profiling early host epigenetic responses in neutrophils may aid in disease recognition. We performed assay for transposase-accessible chromatin (ATAC)-seq of human neutrophils challenged with six toll-like receptor ligands and two organisms; and RNA-seq after Escherichia coli exposure for 1 and 4 h along with ATAC-seq. ATAC-seq of neutrophils facilitates detection of pathogen DNA. In addition, despite similarities in genomic distribution of differential chromatin changes across challenges, only a fraction overlaps between the challenges. Ligands depict shared signatures, but majority are unique in position, function, and challenge. Epigenomic changes are plastic, only ∼120 are shared by Ecoli challenges over time, resulting in varied differential genes and associated processes. We identify three classes of gene regulation, chromatin access changes in the promoter; changes in the promoter and distal enhancers; and controlling expression through changes solely in distal enhancers. These and transcription factor footprinting reveal timely and challenge specific mechanisms of transcriptional regulation in neutrophils.

中文翻译：

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通过敏感的病原体检测分析人类中性粒细胞中染色质可及性反应。

败血症、血流感染和宿主反应失调的后遗症是全球死亡的主要原因。中性粒细胞严格调节对病原体的反应，以防止器官损伤。分析嗜中性粒细胞中的早期宿主表观遗传反应可能有助于疾病识别。我们对受到六种 toll 样受体配体和两种生物体攻击的人类中性粒细胞进行转座酶可及染色质 (ATAC)-seq 分析；和大肠杆菌后的 RNA-seq与 ATAC-seq 一起暴露 1 和 4 小时。中性粒细胞的 ATAC-seq 有助于检测病原体 DNA。此外，尽管不同挑战之间染色质差异变化的基因组分布相似，但挑战之间只有一小部分重叠。配体描绘了共享的签名，但大多数在位置、功能和挑战上都是独一无二的。表观基因组变化是可塑性的，大肠杆菌仅共享 ∼120个随着时间的推移，挑战，导致不同的差异基因和相关过程。我们确定了三类基因调控，启动子中的染色质访问变化；启动子和远端增强子的变化；并通过仅在远端增强子中的变化来控制表达。这些和转录因子足迹揭示了及时和挑战中性粒细胞转录调控的特定机制。