Epigenetic modulation of effector T cells The epigenetic states and associated chromatin dynamics underlying the initiation and maintenance of memory and effector CD8+ T cells are poorly understood. Pace et al. found that mice lacking the histone H3 lysine 9 methyltransferase Suv39h1 had markedly reduced antigen-specific effector CD8+ T cell responses to Listeria monocytogenes infection (see the Perspective by Henning et al.). Instead, CD8+ T cells in these mice were enriched for genes associated with naïve and memory signatures and showed enhanced memory potential and increased survival capacity. Thus, Suv39h1 marks chromatin through H3K9me3 deposition and silences memory and stem cell programs during the terminal differentiation of effector CD8+ T cells. Science, this issue p. 177; see also p. 163 Suv39h1 silences stem/memory gene expression during effector CD8+ T cell differentiation. 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 Listeria monocytogenes 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 Suv39h1-defective T cell effectors. As a result, Suv39h1-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.

中文翻译：

---

CD8+T细胞命运承诺中干性的表观遗传控制

效应 T 细胞的表观遗传调节 对记忆和效应 CD8+ T 细胞启动和维持的表观遗传状态和相关染色质动力学知之甚少。佩斯等人。发现缺乏组蛋白 H3 赖氨酸 9 甲基转移酶 Suv39h1 的小鼠对单核细胞增生李斯特菌感染的抗原特异性效应子 CD8+ T 细胞反应显着降低（参见 Henning 等人的观点）。相反，这些小鼠中的 CD8+ T 细胞富含与幼稚和记忆特征相关的基因，并显示出增强的记忆潜力和增加的生存能力。因此，Suv39h1 通过 H3K9me3 沉积标记染色质，并在效应 CD8+ T 细胞的终末分化过程中沉默记忆和干细胞程序。科学，这个问题 p。177; 另见第。163 Suv39h1 在效应 CD8+ T 细胞分化过程中沉默干/记忆基因表达。启动后，幼稚的 CD8+ T 淋巴细胞建立特定的可遗传转录程序，这些程序定义了向持久记忆细胞或短寿命效应细胞的进展。尽管谱系规范对于保护至关重要，但染色质动力学如何有助于控制基因表达程序仍不清楚。我们探索了组蛋白甲基转移酶 Suv39h1 基因沉默的作用。在单核细胞增生李斯特菌感染后激活的小鼠 CD8+ T 细胞中，组蛋白 H3 赖氨酸 9 的 Suv39h1 依赖性三甲基化控制着一组干细胞相关记忆基因的表达。单细胞 RNA 测序揭示了在 Suv39h1 缺陷 T 细胞效应器中选择性沉默干/记忆基因的缺陷。因此，Suv39h1 缺陷型 CD8+ T 细胞显示出持续存活和增加的长期记忆重编程能力。因此，Suv39h1 在标记染色质以在 CD8+ T 效应子终末分化过程中沉默茎/记忆基因方面发挥着关键作用。