title: Global DNA methylation remodeling accompanies CD8 T cell effector function.
abstract: The differentiation of CD8 T cells in response to acute infection results in the acquisition of hallmark phenotypic effector functions; however, the epigenetic mechanisms that program this differentiation process on a genome-wide scale are largely unknown. In this article, we report the DNA methylomes of Ag-specific naive and day-8 effector CD8 T cells following acute lymphocytic choriomeningitis virus infection. During effector CD8 T cell differentiation, DNA methylation was remodeled such that changes in DNA methylation at gene promoter regions correlated negatively with gene expression. Importantly, differentially methylated regions were enriched at cis-elements, including enhancers active in naive T cells. Differentially methylated regions were associated with cell type-specific transcription factor binding sites, and these transcription factors clustered into modules that define networks targeted by epigenetic regulation and control of effector CD8 T cell function. Changes in the DNA methylation profile following CD8 T cell activation revealed numerous cellular processes, cis-elements, and transcription factor networks targeted by DNA methylation. Together, the results demonstrated that DNA methylation remodeling accompanies the acquisition of the CD8 T cell effector phenotype and repression of the naive cell state. Therefore, these data provide the framework for an epigenetic mechanism that is required for effector CD8 T cell differentiation and adaptive immune responses.
authors: Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
authors: Christopher D
authors: CD
authors: Scharer
authors: Benjamin G
authors: BG
authors: Barwick
authors: Benjamin A
authors: BA
authors: Youngblood
authors: Rafi
authors: R
authors: Ahmed
authors: Jeremy M
authors: JM
authors: Boss
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D019175:DNA Methylation / Q000235:genetics* / Q000276:immunology; D044127:Epigenesis, Genetic / Q000235:genetics* / Q000276:immunology; D047468:Immunoprecipitation; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data
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