The histone methyltransferase G9a is required for silencing of helper T lineage genes in CD8 T cells. Mus musculus strain:C57B6

Alternative cell lineages that share a common precursor require the stable silencing of the opposing lineage's genes, which is mediated by constitutive activity of transcription factors or the actions of epigenetic factors. The differentiation of CD4 and CD8 T cells has been used as a model system for studying the requirements of transcription and epigenetic factors during fate decision processes. Here we show that the histone methyltransferase G9a is necessary for heritable silencing of Cd4 and other helper T lineage genes in CD8 T cells. Despite normal Cd4 downregulation during development, G9a-deficient CD8 T cells fail to maintain silencing of helper T lineage genes when they repeated divide under non-inflammatory conditions. However Cd4 depression is prevented during division driven by elevated TCR signaling and inflammatory cytokine signaling. Our results reveal the requirement of G9a in silencing helper T lineage genes and that CD8 T cells employ alternative mechanisms to maintain CD8 cellular identity during immune responses.