title: Coordinated changes in DNA methylation in antigen-specific memory CD4 T cells.
abstract: Memory CD4(+) T cells are central regulators of both humoral and cellular immune responses. T cell differentiation results in specific changes in chromatin structure and DNA methylation of cytokine genes. Although the methylation status of a limited number of gene loci in T cells has been examined, the genome-wide DNA methylation status of memory CD4(+) T cells remains unexplored. To further elucidate the molecular signature of memory T cells, we conducted methylome and transcriptome analyses of memory CD4(+) T cells generated using T cells from TCR-transgenic mice. The resulting genome-wide DNA methylation profile revealed 1144 differentially methylated regions (DMRs) across the murine genome during the process of T cell differentiation, 552 of which were associated with gene loci. Interestingly, the majority of these DMRs were located in introns. These DMRs included genes such as CXCR6, Tbox21, Chsy1, and Cish, which are associated with cytokine production, homing to bone marrow, and immune responses. Methylation changes in memory T cells exposed to specific Ag appeared to regulate enhancer activity rather than promoter activity of immunologically relevant genes. In addition, methylation profiles differed between memory T cell subsets, demonstrating a link between T cell methylation status and T cell differentiation. By comparing DMRs between naive and Ag-specific memory T cells, this study provides new insights into the functional status of memory T cells.
authors.affiliation: Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. hashimot@m.u-tokyo.ac.jp
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Katsumi
authors.initials: K
authors.lastname: Ogoshi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sasaki
authors.forename: Jun
authors.initials: J
authors.lastname: Abe
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Budrul
authors.initials: B
authors.lastname: Ahsan
authors.forename: Kenshiro
authors.initials: K
authors.lastname: Oshima
authors.forename: Francis H W
authors.initials: FH
authors.lastname: Shand
authors.forename: Akio
authors.initials: A
authors.lastname: Ametani
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Takashi
authors.initials: T
authors.lastname: Wada
authors.forename: Masahira
authors.initials: M
authors.lastname: Hattori
authors.forename: Sumio
authors.initials: S
authors.lastname: Sugano
authors.forename: Shinichi
authors.initials: S
authors.lastname: Morishita
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019175:DNA Methylation / Q000235:genetics*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D007156:Immunologic Memory / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D059467:Transcriptome
chemical_list: D018984:Epitopes, T-Lymphocyte