title: Active demethylation of the IL-2 Promoter in CD4+ T cells is mediated by an inducible DNA glycosylase, Myh.
abstract: 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.
authors.affiliation: Kelly Services, Inc., 1 Church Street, Suite 304, Rockville, MD 20850, USA; Department of Pharmacology, University of Illinois at Chicago, 835 S. Wolcott Street, Chicago, IL 60616, USA. Electronic address: wul@uic.edu.
authors.forename: Liangtang
authors.initials: L
authors.lastname: Wu
authors.affiliation: Kelly Services, Inc., 1 Church Street, Suite 304, Rockville, MD 20850, USA.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D007376:Interleukin-2; D034741:RNA, Small Interfering; D007371:Interferon-gamma; C093335:5-methylcytosine-DNA glycosylase; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase
keywords: CD4+ T cells; DNA glycosylase; Demethylation; IL-2; Myh