IFN-γ suppresses permissive chromatin remodeling in the regulatory region of the Il4 gene.

In order to develop the most effective T helper type-1 (Th1) immunity, naïve CD4(+) T cells must acquire the capacity to express IFN-γ while silencing T helper type-2 (Th2) cytokine-producing potential. An Il4 gene silencer has been described. However, it is not completely understood how the silencer works. In this study, we examine whether IFN-γ can suppress permissive chromatin remodeling of regulatory region of the Il4 gene. We demonstrate that IFN-γ suppresses H3K4 dimethylation at the intronic enhancer region of the Il4 gene. The IFN-γ-mediated suppression of permissive chromatin remodeling is IFN-γ receptor-, STAT1-, and T-bet-dependent. Our study reveals a novel mechanism of how Th1 cells silence the Il4 gene.