Cutting Edge: The Histone Methyltransferase G9a Is Required for Silencing of Helper T Lineage-Associated Genes in Proliferating CD8 T Cells.

Helper versus cytotoxic T lineage decision in the thymus has been studied as a model for silencing of alternative lineage genes. Although the transcription factor RUNX3 is required for the initiation of silencing in developing CD8 T cells， it is unknown how silencing of and other helper T lineage genes is maintained. We show that the histone methyltransferase G9a is necessary for silencing helper T lineage genes in proliferating mouse CD8 T cells. Despite normal initial downregulation， G9a-deficient CD8 T cells derepress and other helper lineage genes during repeated division in lymphopenia or in response to tumor Ag. However， G9a was dispensable for continued silencing of those genes in CD8 T cells that respond to infection by These results demonstrate that G9a facilitates maintenance of cellular identity of CD8 T cells during cell division， which is further reinforced by inflammatory signals.