Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA; email:
Annu Rev Immunol. 2020 Apr 26;38:397-419. doi: 10.1146/annurev-immunol-092719-082622. Epub 2020 Jan 28.
T cell development involves stepwise progression through defined stages that give rise to multiple T cell subtypes, and this is accompanied by the establishment of stage-specific gene expression. Changes in chromatin accessibility and chromatin modifications accompany changes in gene expression during T cell development. Chromatin-modifying enzymes that add or reverse covalent modifications to DNA and histones have a critical role in the dynamic regulation of gene expression throughout T cell development. As each chromatin-modifying enzyme has multiple family members that are typically all coexpressed during T cell development, their function is sometimes revealed only when two related enzymes are concurrently deleted. This work has also revealed that the biological effects of these enzymes often involve regulation of a limited set of targets. The growing diversity in the types and sites of modification, as well as the potential for a single enzyme to catalyze multiple modifications, is also highlighted.
T 细胞的发育涉及通过定义明确的阶段逐步进展，从而产生多种 T 细胞亚型，这伴随着特定阶段基因表达的建立。在 T 细胞发育过程中，染色质可及性和染色质修饰的变化伴随着基因表达的变化。在整个 T 细胞发育过程中，添加或逆转 DNA 和组蛋白上的共价修饰的染色质修饰酶在基因表达的动态调控中起着关键作用。由于每个染色质修饰酶都有多个家族成员，这些家族成员通常在 T 细胞发育过程中同时表达，因此只有当两个相关的酶同时被删除时，它们的功能才会显现出来。这项工作还揭示了这些酶的生物学效应通常涉及对有限数量的靶标的调节。越来越多的修饰类型和修饰位点，以及单个酶能够催化多种修饰的可能性，也得到了强调。
