Lineage relationship of CD8(+) T cell subsets is revealed by progressive changes in the epigenetic landscape.
Lineage relationship of CD8(+) T cell subsets is revealed by progressive changes in the epigenetic landscape.
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CD8（+）T细胞亚群的谱系关系通过表观遗传景观的进行性变化揭示。
DOI：
10.1038/cmi.2015.32
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发表时间：
2016-07
影响因子：
24.1
通讯作者：
Restifo NP
中科院分区：
文献类型：
--
作者：
Crompton JG;Narayanan M;Cuddapah S;Roychoudhuri R;Ji Y;Yang W;Patel SJ;Sukumar M;Palmer DC;Peng W;Wang E;Marincola FM;Klebanoff CA;Zhao K;Tsang JS;Gattinoni L;Restifo NP
为了更好地阐明与T细胞分化后观察到的动态基因表达程序相关的表观遗传机制，我们研究了幼稚和记忆CD 8 + T细胞中组蛋白修饰的基因组景观。使用ChIP-Seq方法结合全局基因表达谱分析，我们在幼稚T记忆干细胞、中枢记忆细胞和效应记忆细胞中生成了全基因组蛋白H3赖氨酸4（H3 K4 me 3）和H3赖氨酸27（H3 K27 me 3）三甲基化图谱，以深入了解组蛋白结构在T细胞分化过程中是如何重塑的。我们发现，H3 K4 me 3组蛋白修饰与基因的激活相关，而H3 K27 me 3与典型基因座的基因表达呈负相关，与T细胞代谢，效应功能和记忆相关的增强子。我们的研究结果还揭示了组蛋白修饰和基因表达特征，这些特征将最近鉴定的T记忆干细胞与其他CD 8 + T细胞亚群区分开来。综上所述，我们的研究结果表明，CD 8+淋巴细胞进行染色质重塑在一个渐进的方式。这些发现对我们理解外周T细胞个体发育和免疫记忆的形成具有重要意义。
To better elucidate epigenetic mechanisms that correlate with the dynamic gene expression program observed upon T-cell differentiation, we investigated the genomic landscape of histone modifications in naive and memory CD8+ T cells. Using a ChIP-Seq approach coupled with global gene expression profiling, we generated genome-wide histone H3 lysine 4 (H3K4me3) and H3 lysine 27 (H3K27me3) trimethylation maps in naive, T memory stem cells, central memory cells, and effector memory cells in order to gain insight into how histone architecture is remodeled during T cell differentiation. We show that H3K4me3 histone modifications are associated with activation of genes, while H3K27me3 is negatively correlated with gene expression at canonical loci and enhancers associated with T-cell metabolism, effector function, and memory. Our results also reveal histone modifications and gene expression signatures that distinguish the recently identified T memory stem cells from other CD8+ T-cell subsets. Taken together, our results suggest that CD8+ lymphocytes undergo chromatin remodeling in a progressive fashion. These findings have major implications for our understanding of peripheral T-cell ontogeny and the formation of immunological memory.