Exploration of the Effect on Genome-Wide DNA Methylation by Knock-Out in Liver.

play an important role in hepatocellular carcinoma and liver fibrosis via inhibiting hepatoma cell proliferation. (), as a target of , regulates the development of primary organic solid tumors through DNA methylation mechanisms. However, the effect of on DNA methylation profiles in liver is unclear. In this study, we used Whole-Genome Bisulfite Sequencing (WGBS) to detect the differentially methylated regions (DMRs), and investigated DMR-related genes and their enriched pathways by . We found that methylated cytosines increased 0.19% in the knock-out (KO) liver fed with high-fat diet (HFD), compared with the wild type (WT). Furthermore, compared with the WT group, the CG methylation patterns of the KO group showed lower CG methylation levels in CG islands (CGIs), promoters and hypermethylation in CGI shores, 5'UTRs, exons, introns, 3'UTRs, and repeat regions. A total of 984 DMRs were identified between the WT and KO groups consisting of 559 hypermethylation and 425 hypomethylation DMRs. Furthermore, DMR-related genes were enriched in metabolism pathways such as carbon metabolism ( () (), arginine and proline metabolism ( (), ()) and purine metabolism ( (). In summary, we are the first to report the change in whole-genome methylation levels by -null through WGBS in liver, and provide an experimental basis for clinical diagnosis and treatment in liver diseases, indicating that may be a potential therapeutic target and biomarker for liver damage-associated diseases and hepatocellular carcinoma.