Interestingly, four of our differentially methylated regions associated with aggression were located within known cytokines regulatory regions. Particularly, three regions lie within Th2 cytokines LCRs, two in the IL-4 loci and one in the IL-10 loci. These LCRs have been shown to have enhancer/insulator activity in Th2 cell differentiation [44], [76], [81]. Changes in chromatin remodeling and DNA methylation in this region are involved in regulating expression of IL-4 and IL-13 during Th2 differentiation [44], [81]. It was previously proposed that DNA demethylation is required for the maintenance of IL-4 LCR enhancer activity in Th2 differentiated cells [81]. STAT6 transcription factor was also shown to be required for the remodeling of this LCR during Th2 cell differentiation [81]. We observed in the same region lower methylation in the CPA individuals in T cells and overall lower IL-4 plasma levels compared to controls (Figure 2A). Since we did not examine the methylation levels in specific T cells subpopulations, we don’t know what this demethylation in CPA individuals means in term of Th2 LCR activity. The fact that it occurs in this
