Genome-wide DNA methylation profiling of human CD4+ T helper cells define epigenetic signatures for Th1, Th17 and non-classic Th1 cells
Naive CD4+ T cells are highly plastic cells that - upon activation - can differentiate into various T helper (Th) cell fates characterized by the expression of specific transcription factors and effector cytokines. Their expression can be stabilized by epigenetic mechanisms including DNA methylation. So far, our knowledge about the link between DNA methylation and T helper cell differentiation processes is fragmentary. In this study, we generated methylomes of CD4+ T helper cells by performing a whole-genome bisulfite sequencing analysis of ex vivo isolated human naïve T cells and selected clones of Th1, non-classic Th1 and Th17 cells. The pairwise comparison of the methylomes identified differentially methylated regions (DMRs) mainly located within introns, followed by promoter regions and exons. In accordance with literature, several DMRs were identified within lineage-specific loci like IFNG, TBX21, IL-17A and RORC. Thus, the identified DMRs are suitable to further characterize the T helper lineages and might be helpful to define lineage-specific regulatory modules involved in human T helper cell differentiation. Overall design: Whole-genome bisulfite sequencing (WGBS) of human ex vivo isolated naive T cells and Th1, Th17 and non-classic Th1 cell clones.