Identification of a novel enhancer essential forSatb1expression in TH2 cells and activated ILC2s

Abstract

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 howSatb1gene 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 acis-regulatory enhancer, essential for maintainingSatb1expression specifically in TH2 cells. This enhancer is occupied by STAT6 and interacts withSatb1promoters through chromatin looping in TH2 cells. Reduction ofSatb1expression, by the lack of this enhancer, resulted in elevated IL-5 expression in TH2 cells. In addition, we found thatSatb1is induced in activated group 2 innate lymphoid cells (ILC2s) through this enhancer. Collectively, these results provide novel insights into howSatb1expression is regulated in TH2 cells and ILC2s during type 2 immune responses.