ATAC-seq of Satb1 conditional KO in CD4+ naïve T cells reveals epigenetic role of Satb1 in developing Th17 T cells by controlling the accessibility of Il2, thereby inhibiting IL-2 signaling in the initial stages of T cell differentiation.
TH17 cells play an important role in host defense especially in barrier organs. Altered functionality of TH17 cells is associated with dysregulated tissue homeostasis resulting in an increased susceptibility for the development of autoimmune diseases. Thus, it is critical to identify mechanisms governing physiological as well as pathophysiological TH17 cell differentiation and identify strategies targeting TH17 cell differentiation in disease settings. Here, we identified the genome organizer Special AT-rich sequence-binding protein 1 (Satb1) as a pioneering factor for TH17 cell development. Satb1 is highly expressed in TH17 cells and loss of Satb1 prevents the differentiation of TH17 cells. As a consequence, expression of Satb1 in CD4+ T cells is required for the formation of TH17 cell-driven autoimmune diseases. Mechanistically, Satb1 mediates TH17 cell development through regulating accessibility of the Il2 gene locus and thereby preventing IL-2 signaling early during TH17 cell differentiation. Thus, Satb1 is critical by suppressing IL-2 expression during the formation of TH17 cells and may be a novel therapeutic target for the treatment of TH17 cell-driven autoimmune diseases. Overall design: ATAC-Seq was performed following Buenrostro et al., 2013 comparing 5 conditional KO samples of naive CD3+CD4+CD25-CD44low/-CD62L+ T cells from Satb1fl/fl x CD4-CreERT2wt/+  mice treated with tamoxifen to 5 untreated (WT) samples of of naive CD3+CD4+CD25-CD44low/-CD62L+ T cells from Satb1fl/fl x CD4-CreERT2wt/+  mice.