ATF7ip targets transposable elements for H3K9me3 deposition to modify CD8+ T cell effector and memory responses [ChIP-seq]

CD8+ T cells are critical for the adaptive immune response to infection and tumors. Moreover, CD8+ T cell memory is important for the immune systems response to repeat infections. Here, we identify the activating transcription factor 7 interacting protein as a critical regulator of CD8+ T cell memory and effector responses. Mice with a T cell specific deletion of ATF7ip have a CD8+ T cell intrinsic enhancement of Il7r expression and Il2 expression leading to enhanced memory responses. ChIP-seq studies identified ATF7ip as an inhibitor of Il7r and Il2 gene expression through the deposition of the repressive histone mark H3K9me3 in the Il7r gene loci and Il2-Il21 intergenic region. Interestingly, ATF7ip targeted transposable elements (TE) for H3K9me3 in these regions. These results demonstrate a new epigenetic pathway by which IL7r and IL-2 production are constrained in CD8+ T cells, and this may open up new avenues for modulating their production. Overall design: Naïve CD8 T cells were isolated by flow cytometry and H3K9me3 ChIP-seq was performed in duplicate CD8Cre/ATF7ip+/fl vs CD8-Cre/ATF7ipfl/fl naïve T cells