title: Defining CD4 T cell memory by the epigenetic landscape of CpG DNA methylation.
abstract: Memory T cells are primed for rapid responses to Ag; however, the molecular mechanisms responsible for priming remain incompletely defined. CpG methylation in promoters is an epigenetic modification, which regulates gene transcription. Using targeted bisulfite sequencing, we examined methylation of 2100 genes (56,000 CpGs) mapped by deep sequencing of T cell activation in human naive and memory CD4 T cells. Four hundred sixty-six CpGs (132 genes) displayed differential methylation between naive and memory cells. Twenty-one genes exhibited both differential methylation and gene expression before activation, linking promoter DNA methylation states to gene regulation; 6 of 21 genes encode proteins closely studied in T cells, whereas 15 genes represent novel targets for further study. Eighty-four genes demonstrated differential methylation between memory and naive cells that correlated to differential gene expression following activation, of which 39 exhibited reduced methylation in memory cells coupled with increased gene expression upon activation compared with naive cells. These reveal a class of primed genes more rapidly expressed in memory compared with naive cells and putatively regulated by DNA methylation. These findings define a DNA methylation signature unique to memory CD4 T cells that correlates with activation-induced gene expression.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: H Kiyomi
authors.initials: HK
authors.lastname: Komori
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Traver
authors.initials: T
authors.lastname: Hart
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: LaMere
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Pamela V
authors.initials: PV
authors.lastname: Chew
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037 dsalomon@scripps.edu.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Salomon
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018899:CpG Islands / Q000235:genetics / Q000276:immunology*; D019175:DNA Methylation / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D044127:Epigenesis, Genetic / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000276:immunology; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology; D017423:Sequence Analysis, RNA / Q000379:methods