Genomic distribution and functional enrichment of differentially methylated genes.

(A) PEA treatment reduced Pcyt2^+ /- DMGs by 96.7% from 5226 to 175 DMGs in Pcyt2^+ /- + PEA with 43% and 57% hyper- and hypomethylated DMGs, respectively, this shows a similar distribution to Pcyt2^+ /- showing a coordinated action of methylation and demethylation processes. (B) DMG distribution across chromosomes showing the highest relative proportions of hypermethylated genes PEA at Chromosomes 1, 2, 3, 8, 11 and 13 (6.4-9.2%) and the highest proportions of hypomethylated genes at Chromosomes 2, 5, 7, 8, 11, and 15 (7.1-14%). (C) Enrichment analysis of DMG in Pcyt2^+ /- + PEA mice showing nearly all enriched pathways were abolished by PEA treatment (D) PEA treatment reduced genes that are differently methylated and expressed (DMEGs) by 95.2% from 162 to 8. Correlation plot of the remaining 8 DMEGs after PEA treatment. Only one gene, Aida, was differentially methylated in promoter region. (E) PCR validation of key genes that were differentially methylated and differentially expressed (Man2a1, Foxo1 and Ndufv2) showing that the expressions of all genes were attenuated by PEA treatment. Band intensities were measured using ImageJ. * p <  0.05, ***p <  0.001.