The Methyltransferase DOT1L Controls Activation and Lineage Integrity in CD4 T Cells during Infection and Inflammation.
Sebastian Scheer, Jessica Runting, Michael Bramhall, Brendan Russ, Aidil Zaini, Jessie Ellemor, Grace Rodrigues, Judy Ng, Colby Zaph
Cell Reports | Published : 2020
CD4+ T helper (Th) cell differentiation is controlled by lineage-specific expression of transcription factors and effector proteins, as well as silencing of lineage-promiscuous genes. Lysine methyltransferases (KMTs) comprise a major class of epigenetic enzymes that are emerging as important regulators of Th cell biology. Here, we show that the KMT DOT1L regulates Th cell function and lineage integrity. DOT1L-dependent dimethylation of lysine 79 of histone H3 (H3K79me2) is associated with lineage-specific gene expression. However, DOT1L-deficient Th cells overproduce IFN-γ under lineage-specific and lineage-promiscuous conditions. Consistent with the increased IFN-γ response, mice with a T-c..View full abstract