Active demethylation of the IL-2 Promoter in CD4+ T cells is mediated by an inducible DNA glycosylase, Myh

Epigenetic control of tissue-specific gene expression is often achieved by active demethylation of promoter regions; however, the nature of all the enzymes mediating this remodeling process is not fully clear. Here we describe a 5-methylcytosine glycosylase activity for the murine DNA base excision repair enzyme Myh and show that it is critically involved in remodeling the IL-2 Promoter for transcription. The enzyme is not expressed in naïve CD4+ T cells, but can be transiently induced following T cell activation. T cells deficient in Myh had blunted demethylation of the promoter and impaired IL-2 secretion but not IFN-γ. An in vitro assay for the glycosylase activity revealed the enzyme to be sequence specific for certain CpG sites in the IL-2 Promoter. These results suggest that DNA demethylation is being selectively used to orchestrate a part of the naïve CD4+ T cell differentiation program.