Institut Curie, PSL Research University, F-75005 Paris, France.
INSERM U932, Equipes Labellisées Ligue contre le Cancer, F-75005 Paris, France.
Science. 2018 Jan 12;359(6372):177-186. doi: 10.1126/science.aah6499.
After priming, naïve CD8 T lymphocytes establish specific heritable transcription programs that define progression to long-lasting memory cells or to short-lived effector cells. Although lineage specification is critical for protection, it remains unclear how chromatin dynamics contributes to the control of gene expression programs. We explored the role of gene silencing by the histone methyltransferase Suv39h1. In murine CD8 T cells activated after infection, Suv39h1-dependent trimethylation of histone H3 lysine 9 controls the expression of a set of stem cell-related memory genes. Single-cell RNA sequencing revealed a defect in silencing of stem/memory genes selectively in -defective T cell effectors. As a result, -defective CD8 T cells show sustained survival and increased long-term memory reprogramming capacity. Thus, Suv39h1 plays a critical role in marking chromatin to silence stem/memory genes during CD8 T effector terminal differentiation.
在启动后，幼稚的 CD8 T 淋巴细胞建立特定的可遗传转录程序，这些程序定义了向长期记忆细胞或短期效应细胞的进展。尽管谱系特化对于保护至关重要，但尚不清楚染色质动力学如何有助于控制基因表达程序。我们探讨了组蛋白甲基转移酶 Suv39h1 对基因沉默的作用。在 感染后激活的小鼠 CD8 T 细胞中，组蛋白 H3 赖氨酸 9 的 Suv39h1 依赖性三甲基化控制了一组与干细胞相关的记忆基因的表达。单细胞 RNA 测序显示，在 -缺陷型 T 细胞效应器中，干细胞/记忆基因的沉默缺陷选择性地出现。结果，-缺陷型 CD8 T 细胞表现出持续的存活和增加的长期记忆重编程能力。因此，Suv39h1 在 CD8 T 效应器终末分化过程中标记染色质以沉默干细胞/记忆基因方面发挥着关键作用。
