Department of Physics, The George Washington University, Washington, DC 20052.
Center for Discovery and Innovation, Hackensack University Medical Center, Nutley, NJ 07110.
Proc Natl Acad Sci U S A. 2023 Dec 19;120(51):e2313476120. doi: 10.1073/pnas.2313476120. Epub 2023 Dec 12.
CD62L central memory CD8 T (T) cells provide enhanced protection than naive cells; however, the underlying mechanism, especially the contribution of higher-order genomic organization, remains unclear. Systematic Hi-C analyses reveal that antigen-experienced CD8 T cells undergo extensive rewiring of chromatin interactions (ChrInt), with T cells harboring specific interaction hubs compared with naive CD8 T cells, as observed at cytotoxic effector genes such as and . T cells also acquire de novo CTCF (CCCTC-binding factor) binding sites, which are not only strongly associated with T-specific hubs but also linked to increased activities of local gene promoters and enhancers. Specific ablation of CTCF in T cells impairs rapid induction of genes in cytotoxic program, energy supplies, transcription, and translation by recall stimulation. Therefore, acquisition of CTCF binding and ChrInt hubs by T cells serves as a chromatin architectural basis for their transcriptomic dynamics in primary response and for imprinting the code of "recall readiness" against secondary challenge.
CD62L 中央记忆 CD8 T（T）细胞提供比幼稚细胞更强的保护；然而，潜在的机制，特别是更高阶基因组组织的贡献，仍然不清楚。系统的 Hi-C 分析显示，抗原经验的 CD8 T 细胞经历染色质相互作用（ChrInt）的广泛重排，与幼稚 CD8 T 细胞相比，T 细胞具有特定的相互作用枢纽，如在细胞毒性效应基因如 和 中观察到的那样。T 细胞还获得新的 CTCF（CCCTC 结合因子）结合位点，这些位点不仅与 T 特异性枢纽强烈相关，而且与局部基因启动子和增强子活性的增加相关。在 T 细胞中特异性缺失 CTCF 会损害细胞毒性程序、能量供应、转录和翻译的快速诱导基因，通过回忆刺激。因此，T 细胞获得 CTCF 结合和 ChrInt 枢纽作为其在初级反应中转录组动力学的染色质结构基础，并为针对二次挑战的“回忆准备”代码印迹。
