CD8(+) T Cells Utilize Highly Dynamic Enhancer Repertoires and Regulatory Circuitry in Response to Infections.
CD8(+) T Cells Utilize Highly Dynamic Enhancer Repertoires and Regulatory Circuitry in Response to Infections.
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DOI：
10.1016/j.immuni.2016.11.009
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发表时间：
2016-12-20
期刊：
影响因子：
32.4
通讯作者：
Xue HH
中科院分区：
文献类型：
--
作者：
He B;Xing S;Chen C;Gao P;Teng L;Shan Q;Gullicksrud JA;Martin MD;Yu S;Harty JT;Badovinac VP;Tan K;Xue HH
效应和记忆 CD8+ T 细胞的分化伴随着转录组和基因启动子处组蛋白修饰的广泛变化；然而，增强子库和相关基因调控网络的定义不明确。使用组蛋白标记染色质免疫沉淀结合深度测序，我们绘制了 LCMV 感染期间抗原特异性幼稚细胞、分化效应细胞和中央记忆 CD8+ T 细胞中的增强子和超级增强子图谱。基于表观基因组学的注释揭示了高度动态的增强子库，这些增强子在 CD8+ T 细胞反应过程中被遗传、从头激活、退役和重新激活。我们采用计算算法将增强子与靶基因启动子配对。平均而言，每个增强子针对三个启动子，每个启动子由两个增强子调节。通过识别增强子中富集的转录因子基序，我们定义了每个 CD8+ T 细胞反应阶段的转录调控电路。这些多维数据集为描绘 CD8+ T 细胞功能分化的分子机制提供了蓝图。他等人。进行了全面的表观基因组分析，并绘制了 CD8+ T 细胞对感染反应期间活性增强子和超级增强子的高度动态库。综合分析揭示了调节电路的广泛重新布线，并在从幼稚 CD8+ T 细胞向效应和记忆 CD8+ T 细胞的转变过程中确定了调节因子。
Differentiation of effector and memory CD8+ T cells is accompanied by extensive changes in the transcriptome and histone modifications at gene promoters; however, the enhancer repertoire and associated gene regulatory networks are poorly defined. Using histone mark chromatin immunoprecipitation coupled with deep sequencing, we mapped the enhancer and super-enhancer landscapes in antigen-specific naïve, differentiated effector, and central memory CD8+ T cells during LCMV infection. Epigenomics-based annotation revealed a highly dynamic repertoire of enhancers, which were inherited, de novo activated, decommissioned and re-activated during CD8+ T cell responses. We employed a computational algorithm to pair enhancers with target gene promoters. On average, each enhancer targeted three promoters and each promoter was regulated by two enhancers. By identifying enriched transcription factor motifs in enhancers, we defined transcriptional regulatory circuitries at each CD8+ T-cell response stage. These multi-dimensional datasets provide a blueprint for delineating molecular mechanisms underlying functional differentiation of CD8+ T cells. He et al. performed comprehensive epigenomic profiling and mapped a highly dynamic repertoire of active enhancers and super enhancers during CD8+ T cell responses to infection. Integrative analyses revealed extensive re-wiring of regulatory circuits and identified regulators during the transition from naïve to effector and memory CD8+ T cells.