Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences(IMS), Yokohama, Japan.
Laboratory for Innate Immune Systems, RIKEN Center for Integrative Medical Sciences(IMS), Yokohama, Japan.
Life Sci Alliance. 2023 May 16;6(8). doi: 10.26508/lsa.202301897. Print 2023 Aug.
The genome organizer, special AT-rich binding protein-1 (SATB1), functions to globally regulate gene networks during primary T cell development and plays a pivotal role in lineage specification in CD4 helper-, CD8 cytotoxic-, and FOXP3 regulatory-T cell subsets. However, it remains unclear how gene expression is controlled, particularly in effector T cell function. Here, by using a novel reporter mouse strain expressing SATB1-Venus and genome editing, we have identified a -regulatory enhancer, essential for maintaining expression specifically in T2 cells. This enhancer is occupied by STAT6 and interacts with promoters through chromatin looping in T2 cells. Reduction of expression, by the lack of this enhancer, resulted in elevated IL-5 expression in T2 cells. In addition, we found that is induced in activated group 2 innate lymphoid cells (ILC2s) through this enhancer. Collectively, these results provide novel insights into how expression is regulated in T2 cells and ILC2s during type 2 immune responses.
基因组组织者，富含特殊 AT 的结合蛋白-1（SATB1），在初始 T 细胞发育过程中发挥全局调控基因网络的作用，并在 CD4 辅助性 T 细胞、CD8 细胞毒性 T 细胞和 FOXP3 调节性 T 细胞亚群的谱系特化中发挥关键作用。然而，基因表达是如何被调控的，特别是在效应 T 细胞功能中，仍不清楚。在这里，我们使用一种新型的表达 SATB1-Venus 的报告小鼠品系和基因组编辑，鉴定了一个 - 调控增强子，它对于维持 T2 细胞中 SATB1 的表达是必需的。这个增强子被 STAT6 占据，并在 T2 细胞中通过染色质环化与 SATB1 启动子相互作用。由于缺乏这个增强子，SATB1 的表达减少导致 T2 细胞中 IL-5 表达的升高。此外，我们发现这个增强子在活化的 2 型固有淋巴细胞（ILC2）中诱导 SATB1 的表达。总之，这些结果为 SATB1 在 2 型免疫反应中 T2 细胞和 ILC2 中的表达调控提供了新的见解。
