Epigenetic repression is required for the generation of CD8+ effector T cells Functional diversity in multicellular organisms is achieved through the differentiation of stem cells. During this process, stem cells must retain both the capacity for self-renewal and the ability to differentiate into highly specialized cell types to produce a diverse array of tissues, each with distinct functions and organization. This plasticity is achieved through alterations to the epigenome, heritable and reversible modifications to DNA and histones that affect chromatin structure and gene transcription without altering the DNA sequence itself. Alterations to the epigenome enable cell type–specific transcriptional control that can change dynamically over the life of a cell. Such flexibility and responsiveness are instrumental in directing gene expression changes throughout cellular differentiation and lineage specification. The acquisition of more specialized functions during differentiation requires not only that the epigenome turn “on” genes involved in lineage commitment, it also necessitates that genes associated with stemness are simultaneously turned “off” (1). On page 177 of this issue, Pace et al. (2) demonstrate that this phenomenon exists in CD8+ T cells, in which epigenetic repression of stemness-associated genes by the histone methyltransferase SUV39H1 is required for T cell effector differentiation. Understanding these mechanisms addresses important questions in immunology and is applicable to cancer immunotherapy.

中文翻译：

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沉默 T 细胞分化中的干性


表观遗传抑制是 CD8+ 效应 T 细胞生成所必需的。多细胞生物的功能多样性是通过干细胞的分化实现的。在此过程中，干细胞必须保留自我更新的能力和分化成高度特化的细胞类型的能力，以产生多种组织，每种组织具有不同的功能和组织。这种可塑性是通过改变表观基因组、对 DNA 和组蛋白进行可遗传和可逆的修饰来实现的，这些修饰会影响染色质结构和基因转录，而不改变 DNA 序列本身。表观基因组的改变使得细胞类型特异性的转录控制能够在细胞的整个生命周期中动态变化。这种灵活性和响应能力有助于指导整个细胞分化和谱系规范中的基因表达变化。在分化过程中获得更专门的功能不仅需要表观基因组“打开”涉及谱系定型的基因，还需要同时“关闭”与干性相关的基因 (1)。在本期第 177 页，Pace 等人。 (2) 证明这种现象存在于 CD8+ T 细胞中，其中组蛋白甲基转移酶 SUV39H1 对干性相关基因的表观遗传抑制是 T 细胞效应分化所需的。了解这些机制可以解决免疫学中的重要问题，并且适用于癌症免疫治疗。