Santosa Endi K, Lau Colleen M, Sahin Merve, Leslie Christina S, Sun Joseph C
bioRxiv. 2023 Jan 19:2023.01.16.524322. doi: 10.1101/2023.01.16.524322.
Immune cells responding to pathogens undergo molecular changes that are intimately linked to genome organization. Recent work has demonstrated that natural killer (NK) and CD8 T cells experience substantial transcriptomic and epigenetic rewiring during their differentiation from naïve to effector to memory cells. Whether these molecular adaptations are accompanied by changes in three-dimensional (3D) chromatin architecture is unknown. In this study, we combine histone profiling, ATAC-seq, RNA-seq and high-throughput chromatin capture (HiC) assay to investigate the dynamics of one-dimensional (1D) and 3D chromatin during the differentiation of innate and adaptive lymphocytes. To this end, we discovered a coordinated 1D and 3D epigenetic remodeling during innate immune memory differentiation, and demonstrate that effector CD8 T cells adopt an NK-like architectural program that is maintained in memory cells. Altogether, our study reveals the dynamic nature of the 1D and 3D genome during the formation of innate and adaptive immunological memory.
对病原体作出反应的免疫细胞会经历与基因组组织密切相关的分子变化。最近的研究表明，自然杀伤（NK）细胞和CD8 T细胞在从幼稚细胞分化为效应细胞再到记忆细胞的过程中，经历了大量的转录组和表观遗传重排。这些分子适应性变化是否伴随着三维（3D）染色质结构的改变尚不清楚。在本研究中，我们结合组蛋白分析、ATAC-seq、RNA-seq和高通量染色质捕获（HiC）分析，以研究先天性和适应性淋巴细胞分化过程中一维（1D）和3D染色质的动态变化。为此，我们发现了先天性免疫记忆分化过程中协调的1D和3D表观遗传重塑，并证明效应CD8 T细胞采用了一种在记忆细胞中维持的NK样结构程序。总之，我们的研究揭示了先天性和适应性免疫记忆形成过程中1D和3D基因组的动态性质。
