Coordinated changes in DNA methylation in antigen-specific memory CD4 T cells
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. While 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. In order to further  elucidate the molecular signature of memory T cells, we conducted methylome and transcriptome analyses in memory CD4+T cells generated using T cells from TCR transgenic mice. The resulting genome-wide DNA methylation profile revealed 1,144 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 antigen 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 antigen-specific memory T cells, this study provides new insights into the functional status of memory T cells.