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Chunk #13 — Results — Associations between Differentially Methylated Regions and Cytokine Levels

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Differential DNA methylation regions in cytokine and transcription factor genomic loci associate with childhood physical aggression.
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The differentially methylated region associated with aggression closest to a cytokine transcription start site was located 2042 bp upstream of the pro-inflammatory cytokine IL-6 and was less methylated in the CPA group compared to controls in T cells (Figure 1A and Figure S1). This region contains a DNAse hypersensitive site and a peak of H3K4Me1 in the two lymphocytes cell lines that were studied in the ENCODE project. Interestingly, this region also coincides with the binding sites of transcription factors PU.1 and NFkB. PU.1 is known to act as both a repressor and activator of several cytokine genes [73] and has been proposed to be involved IL-6 expression [74]. Moreover, this IL-6 upstream region has been previously reported to have basic transcriptional activity in gene reporter luciferase assays [75]. A second region less methylated in the T cells of CPA individuals compared to controls was located in the IL-1α locus (Figure 1B and Figure S1B), located 27 Kb upstream of IL-1α. The region is of interest because its methylation levels are significantly correlated with IL-1α levels (R = 0.52; FDR