Abstract
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.
Highlights
IntroductionThe domestic pig (Sus scrofa), an economically important farm animal, is widely used in biomedical research and comparative genome studies, because of physiological (the organs of the pig are similar in size to those of humans), metabolic, and genomic similarities with humans[1,2,3,4]
The domestic pig (Sus scrofa), an economically important farm animal, is widely used in biomedical research and comparative genome studies, because of physiological, metabolic, and genomic similarities with humans[1,2,3,4]
The DNA methylation pattern around the transcription start site (TSS) showed a V-shaped curve in all three breeds, after a sharp increase in methylation in the 5′-region of the gene body, the methylation level remained relatively constant until the transcription ending site (TES), whereas hypomethylation was observed at the 3′-ends of genes (Fig. 1A)
Summary
The domestic pig (Sus scrofa), an economically important farm animal, is widely used in biomedical research and comparative genome studies, because of physiological (the organs of the pig are similar in size to those of humans), metabolic, and genomic similarities with humans[1,2,3,4]. Another study showed that muscle fiber formation in TC pigs began earlier than muscle fiber formation in Yorkshire pigs, while the muscle maturation process was comparatively more complicated in young Yorkshire piglets[13] These studies have illuminated the genetic basis of the phenotype of skeletal muscle and identified candidate genes related to muscle development. Li et al carried out genome-wide DNA methylation profiling in adipose and skeletal muscle tissues from three pig breeds, revealing that differentially methylated regions in promoters were highly associated with obesity development via repressing expression of known obesity-related genes and novel genes[42]. The mechanisms through which epigenetic regulation influence muscle performance in mammals remain largely unclear; the mechanisms underlying phenotypic variation in skeletal muscle may be revealed by assessing genome-wide DNA methylation signatures together with the transcriptome (including mRNA, lncRNA and miRNA), allowing candidate genes to be identified and assessed in future studies. Our study provides an empirical basis for further development of the domestic pig as a model organism for studies aimed at understanding human growth, obesity, and muscle-related diseases
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