美国国立卫生研究院Han-Yu Shih团队的最新研究表明，快速增强子重塑和转录因子（TF）再利用诱导NK细胞急性激活后基因高效表达。该项研究成果在线发表在2020年10月5日的《免疫》上。

研究人员探究了初始和从头形成增强子如何协调实现急性激活过程中高效的基因诱导。在体外和弓形虫感染模型中，对自然杀伤（NK）细胞中高诱导基因（HIGs）附近区域表观基因组学和转录组学的分析表明，从头合成染色质可及性和增强子重塑受控于信号转导TFs STAT。

急性NK细胞激活使得谱系决定TF T-bet重塑为从头增强子，而与DNA序列特异性基序识别无关。因此，急性刺激通过组合和重塑谱系决定和信号调节TF来改变增强子功能，以确保开启有效的反应。

据介绍，先天性免疫应答受控于调节区域转录因子可及性介导的快速和精准基因调节。在NK细胞和其他先天性淋巴样细胞中，谱系发育过程中功能增强子被活化并形成了从头合成增强子，其表征了激活NK细胞和巨噬细胞中先天记忆的获得。

附：英文原文

Title: Rapid Enhancer Remodeling and Transcription Factor Repurposing Enable High Magnitude Gene Induction upon Acute Activation of NK Cells

Author: Giuseppe Sciumè, Yohei Mikami, Dragana Jankovic, Hiroyuki Nagashima, Alejandro V. Villarino, Tasha Morrison, Chen Yao, Sadie Signorella, Hong-Wei Sun, Stephen R. Brooks, Difeng Fang, Vittorio Sartorelli, Shingo Nakayamada, Kiyoshi Hirahara, Beatrice Zitti, Fred P. Davis, Yuka Kanno, John J. O’Shea, Han-Yu Shih

Issue&Volume: 2020-10-02

Abstract: Innate immune responses rely on rapid and precise gene regulation mediated by accessibilityof regulatory regions to transcription factors (TFs). In natural killer (NK) cellsand other innate lymphoid cells, competent enhancers are primed during lineage acquisition,and formation of de novo enhancers characterizes the acquisition of innate memory in activated NK cells andmacrophages. Here, we investigated how primed and de novo enhancers coordinate to facilitate high-magnitude gene induction during acute activation.Epigenomic and transcriptomic analyses of regions near highly induced genes (HIGs)in NK cells both in vitro and in a model of Toxoplasma gondii infection revealed de novo chromatin accessibility and enhancer remodeling controlled by signal-regulated TFsSTATs. Acute NK cell activation redeployed the lineage-determining TF T-bet to de novo enhancers, independent of DNA-sequence-specific motif recognition. Thus, acute stimulationreshapes enhancer function through the combinatorial usage and repurposing of bothlineage-determining and signal-regulated TFs to ensure an effective response.

DOI: 10.1016/j.immuni.2020.09.008

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30402-7