The IL-8 locus contains eight regions differentially methylated between CPA and controls in monocytes and three in T cells (Figure 3A and Figure S3). Since IL-8 is mainly expressed in monocytes, we focused on two regions more methylated in monocytes of CPA individuals that are 16 Kb and 19 Kb upstream of IL-8, respectively (Figure 3A bottom, highlighted in red). Both regions, though located far from the gene promoter, were found to include a strong DNase hypersensitive cluster, and the second region contained a small H3K4Me1 peak in the K652 cell lines. Interestingly, binding sites of transcriptional activators c-Jun and JunD were identified in the first region. C-Jun and JunD are both part of the AP-1 transcriptional complex, a well-known activator of many genes including cytokines [77].
