Transcriptomic and methylomic analyses of liver tissue in nonalcoholic steatohepatitis [RNA-seq]

Recent studies have shown that DNA methylation is strongly associated with many important biological processes. However, the relationship between DNA methylation and NASH remains poorly understood.In the present study, through WGBS and RNA transcriptome sequencing in high-fructose-high-cholesterol diet for 28 weeks NASH mice, we found that enrichment of DNA methylation dependent DEGs mainly enriched in steroid metabolic process, steroid hormone biosynthesis were significantly down-regulated in NASH group, while those DEGs enriched in negative regulation of cytokine production were significantly up-regulated in NASH group. We identified 992 overlapping and differentially expressed genes (DEGs) that changed at both the mRNA expression level and DNA methylation. Among them, 332 genes displayed DNA methylation dependent changes of mRNA expression, indicating that DNA methylation tend to be positively correlated with NASH development. Taken together, our results demonstrate that DNA methylation may play an important role in the development of NASH. Male C57BL/6J mice aged 8 weeks were purchased from the Shanghai Laboratory Animal Company (SLAC, Shanghai, China). A high-fat-high-cholesterol high-fructose diet was purchased from Research Diets (D09100310, Research Diets Inc, New Brunswick, USA). After a 28-weeks intervention period in which mice were fed either a normal diet (ND) or HFHC, mice were anesthetized with 10% chloral hydrate.