Dynamic redistribution of CTCF demarcates bifurcation of cytotoxic effector and memory precursor programs [ATAC-Seq]

CTCF is known to mediate long range chromatin intearction and 3D genome organization. In CD8+ T cells responding to actue infection, CTCF is redistributed to induce the the cytotoxic program while using its insulation function to suppresss memory precursor fate. Naive P14 TCR transgenic, hCD2-Cre, Rosa26-lsl-GFP, Ctcf wild-type or floxed CD8+ T cells were adoptively transferred into CD45 disparate recipients followed by infection with LCMV Armstrong. On day 4 post infection, P14 cells were sort purified and used for ATAC-seq analysis along with naive cells.

CCCTC结合因子（CTCF）已知可介导长程染色质相互作用与三维基因组组织。在响应急性感染的CD8+ T细胞中，CTCF发生重分布以激活细胞毒性程序，同时通过其染色质绝缘功能抑制记忆前体命运。研究人员将初始P14 T细胞受体转基因、携带hCD2-Cre与Rosa26-lsl-GFP基因型的CTCF野生型或条件性敲除（floxed）CD8+ T细胞过继转移至CD45异型受体小鼠体内，随后以淋巴细胞脉络丛脑膜炎病毒阿姆斯特丹株（LCMV Armstrong）感染受体。感染后第4天，分选纯化P14细胞，并与初始细胞一同开展转座酶可及性测序（ATAC-seq）分析。