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Chunk #10 — Results — Associations of Differential DNA Methylation with Physical Aggression in Cytokine Genes

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Differential DNA methylation regions in cytokine and transcription factor genomic loci associate with childhood physical aggression.
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To better understand the regulatory factors potentially affected by the differentially methylated regions associated with aggression, we compared each differentially methylated region against transcription factor binding sites, DNase clusters and histone mark enrichments recorded in the Encyclopedia of DNA Elements (ENCODE) database (http://genome.ucsc.edu/ENCODE/), derived previously from 24 different cell lines (histone mark profiles were available for only 8 of the cell lines). In total, 25 of the 48 differentially methylated regions associated with CPA coincided with transcription factor binding sites (Table 1), and many of the bound transcription factors are known regulators of cytokines such as NFkB, GR, PU.1, STAT and BAFF family members. A high fraction of the differentially methylated regions associated with aggression (35 of 48) coincided with DNase hypersensitive clusters indicating that these regions have an open chromatin state in at least one cell line and therefore likely to play regulatory roles (Table 1). The number of cell lines in which the DNase clusters were observed is shown in Figures 1, 2, 3 as well as in the Figures S1, S2, S3. Histone marks are included in