Natural Genetic Variation Reveals Key Features of Epigenetic and Transcriptional Memory in Virus-Specific CD8 T Cells.,Immunity

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Natural Genetic Variation Reveals Key Features of Epigenetic and Transcriptional Memory in Virus-Specific CD8 T Cells.
Immunity ( IF 25.5 ) Pub Date : 2019-04-23 , DOI: 10.1016/j.immuni.2019.03.031
Joris van der Veeken ₁ , Yi Zhong ₂ , Roshan Sharma ₃ , Linas Mazutis ₄ , Phuong Dao ₄ , Dana Pe'er ₄ , Christina S Leslie ₄ , Alexander Y Rudensky ₁

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Stable changes in chromatin states and gene expression in cells of the immune system form the basis for memory of infections and other challenges. Here, we used naturally occurring cis-regulatory variation in wild-derived inbred mouse strains to explore the mechanisms underlying long-lasting versus transient gene regulation in CD8 T cells responding to acute viral infection. Stably responsive DNA elements were characterized by dramatic and congruent chromatin remodeling events affecting multiple neighboring sites and required distinct transcription factor (TF) binding motifs for their accessibility. Specifically, we found that cooperative recruitment of T-box and Runx family transcription factors to shared targets mediated stable chromatin remodeling upon T cell activation. Our observations provide insights into the molecular mechanisms driving virus-specific CD8 T cell responses and suggest a general mechanism for the formation of transcriptional and epigenetic memory applicable to other immune and non-immune cells.

中文翻译：

自然遗传变异揭示了病毒特异性 CD8 T 细胞中表观遗传和转录记忆的关键特征。

免疫系统细胞中染色质状态和基因表达的稳定变化构成了对感染和其他挑战的记忆的基础。在这里，我们使用野生衍生的近交系小鼠品系中自然发生的顺式调控变异来探索响应急性病毒感染的 CD8 T 细胞中长期与瞬时基因调控的机制。稳定响应的 DNA 元件的特点是影响多个相邻位点的显着且一致的染色质重塑事件，并且需要不同的转录因子 (TF) 结合基序才能获得它们。具体来说，我们发现 T-box 和 Runx 家族转录因子向共享靶标的协同募集介导了 T 细胞活化后稳定的染色质重塑。

更新日期：2019-04-23

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