First Author | Scheer S | Year | 2020 |
Journal | Cell Rep | Volume | 33 |
Issue | 11 | Pages | 108505 |
PubMed ID | 33326781 | Mgi Jnum | J:298831 |
Mgi Id | MGI:6489203 | Doi | 10.1016/j.celrep.2020.108505 |
Citation | Scheer S, et al. (2020) The Methyltransferase DOT1L Controls Activation and Lineage Integrity in CD4(+) T Cells during Infection and Inflammation. Cell Rep 33(11):108505 |
abstractText | 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-gamma under lineage-specific and lineage-promiscuous conditions. Consistent with the increased IFN-gamma response, mice with a T-cell-specific deletion of DOT1L are susceptible to infection with the helminth parasite Trichuris muris and are resistant to the development of allergic lung inflammation. These results identify a central role for DOT1L in Th2 cell lineage commitment and stability and suggest that inhibition of DOT1L may provide a therapeutic strategy to limit type 2 immune responses. |