DNA methylation plays a pivotal role in biological processes by affecting gene expression. However, how DNA methylation mediates phenotype difference of skeletal muscle between lean-, obese-, and mini-type pigs remains unclear. We systematically carried out comparative analysis of skeletal muscle by integrating analysis of genome-wide DNA methylation, mRNA, lncRNA and miRNA profiles in three different pig breeds (obese-type Tongcheng, lean-type Landrace, and mini-type Wuzhishan pigs). We found that the differentially methylated genes (DMGs) were significantly associated with lipid metabolism, oxidative stress and muscle development. Among the identified DMGs, 253 genes were related to body-size and obesity. A set of lncRNAs and mRNAs including UCP3, FHL1, ANK1, HDAC4, and HDAC5 exhibited inversely changed DNA methylation and expression level; these genes were associated with oxidation reduction, fatty acid metabolism and cell proliferation. Gene regulatory networks involved in phenotypic variation of skeletal muscle were related to lipid metabolism, cellular movement, skeletal muscle development, and the p38 MAPK signaling pathway. DNA methylation potentially influences the propensity for obesity and body size by affecting gene expression in skeletal muscle. Our findings provide an abundant information of epigenome and transcriptome that will be useful for animal breeding and biomedical research.
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