Plasticity of DNA methylation in mouse T cell activation and differentiation

Here, we report on the highly plastic nature of DNA methylation at the genome-wide level as T cells undergo activation, differentiation and aging. Of particular note were the findings that DNA demethylation occurred rapidly following T cell activation and that all differentiated T cell populations displayed lower levels of global methylation than the non-differentiated population. In addition, T cells from older mice had a reduced level of DNA methylation, most likely explained by the increase in the memory/effector cell fraction. Although significant genome-wide changes were observed, changes in DNA methylation at individual genes were restricted to specific cell types. Changes in the expression of enzymes involved in DNA methylation and demethylation reflect in most cases the changes observed in the genome-wide DNA methylation status.We have demonstrated that DNA methylation is dynamic and flexible in CD4+ T cells and changes rapidly both in a genome-wide and in a targeted manner during T cell activation, differentiation. These changes are accompanied by parallel changes in the enzymatic complexes that have been implicated in DNA methylation and demethylation implying that the balance between these opposing activities may play a role in the maintaining the methylation profile of a given cell type but also allow flexibility in a cell population that needs to respond rapidly to environmental signals.DNA methylation is one of the best characterized epigenetic modifications and changes in DNA methylation are associated with many biological processes. In higher organisms, a cell's phenotype, arising from alternative gene expression profiles, can be controlled at least in part by DNA methylation [1]. To date, the most accepted hypothesis is that gene silencing is correlated with DNA methylation at the promoter regions of the genes, while hypomethylation at such regions is linked to gene activation. Genomic DNA methylation is generally stable in somatic cells but is know