De novo DNA methylation by DNA Methyltransferase 3a controls early effector CD8+ T cell fate decisions following activation

ABSTRACT: DNMT3a is a de novo DNA methyltransferase expressed robustly after T cell activation that regulates plasticity of CD4+ T cell cytokine expression. Here we show that DNMT3a is critical for directing early CD8+ T cell effector and memory fate decisions. While effector function of DNMT3a knockout T cells is normal, they develop more memory precursor and fewer terminal effector cells in a T cell intrinsic manner compared to wild-type animals. Rather than increasing plasticity of differentiated effector CD8+ T cells, loss of DNMT3a biases differentiation of early effector cells into memory precursor cells. This is attributed in part to ineffective repression of Tcf1 expression in knockout T cells, as DNMT3a localizes to the Tcf7 promoter and catalyzes its de novo methylation in early effector W

ORGANISM(S): Mus musculus

SUBMITTER: Christopher Gamper 

PROVIDER: E-GEOD-85823 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress