Identification of a novel enhancer essential for expression in T2 cells and activated ILC2s.

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.