Three differentially methylated regions associated with aggression lie within 10 Kb downstream of the IL-10 transcription start site. Two regions are differentially methylated in T cells the first (+6 Kb) is more methylated in CPA individuals whereas the second (+7 Kb) is less methylated. The third difference lies in the 3′UTR of IL-10 and is more methylated in monocytes of CPA individuals (Figure 2B and Figure S2B). Only the first region (+6 Kb) contains several of the ENCODE regulatory elements (Figure 2B bottom, highlighted in blue), including a strong DNase hypersensitive cluster, enrichment for histone marks and several transcription factor binding sites. Interestingly, this region was previously found to have promoter/enhancer activity in Th2 cells and was proposed to function as a LCR for the IL-10 gene locus [76].
