Genome-wide landscape of DNA methylomes and their relationship with mRNA and miRNA transcriptomes in oxidative and glycolytic skeletal muscles

Linyuan Shen,Guoqing Tang,Shunhua Zhang,Yudong Xia,Jingjing Du,Yuhua Fu,Qiong Yang,Mingzhou Li,Zhendong Tan,Li Zhu,Xuewei Li,Yanzhi Jiang,Jinyong Wang

doi:10.1038/srep32186

Abstract

The physiological, biochemical and functional differences between oxidative and glycolytic muscles play important roles in human metabolic health and in animal meat quality. To explore these differences, we determined the genome-wide landscape of DNA methylomes and their relationship with the mRNA and miRNA transcriptomes of the oxidative muscle psoas major (PMM) and the glycolytic muscle longissimus dorsi (LDM). We observed the hypo-methylation of sub-telomeric regions. A high mitochondrial content contributed to fast replicative senescence in PMM. The differentially methylated regions (DMRs) in promoters (478) and gene bodies (5,718) were mainly enriched in GTPase regulator activity and signaling cascade-mediated pathways. Integration analysis revealed that the methylation status within gene promoters (or gene bodies) and miRNA promoters was negatively correlated with mRNA and miRNA expression, respectively. Numerous genes were closely related to distinct phenotypic traits between LDM and PMM. For example, the hyper-methylation and down-regulation of HK-2 and PFKFB4 were related to decrease glycolytic potential in PMM. In addition, promoter hypo-methylation and the up-regulation of miR-378 silenced the expression of the target genes and promoted capillary biosynthesis in PMM. Together, these results improve understanding of muscle metabolism and development from genomic and epigenetic perspectives.

Highlights

The distribution of MeDIP-Seq reads along chromosomes and genome features represented a genome-wide methylation pattern (Fig. 2)
The results indicated that differentially methylated regions were present mainly in the gene body, in agreement with the distribution of the DMRs near the gene regions; for example, there were 5,718 DMRs located in the gene body region but only 478 DMRs located in the gene promoter regions (Fig. 4b)
It has previously been reported that HK-2 is positively correlated with glycolytic potential and is less strongly expressed in slow-oxidative-type muscle[49], a result consistent with the present findings that the high methylation status of HK-2 resulted in lower mRNA expression levels in psoas major muscle (PMM) (Fig. 5c)

Summary

Introduction

The distribution of MeDIP-Seq reads along chromosomes and genome features represented a genome-wide methylation pattern (Fig. 2). Differential DNA methylation in the subtelomeric regions and the telomere length of LDM and PMM. This mechanism is consistent with the finding that PMM had a higher mitochondrial content but a lower telomere length than LDM (Figs 1e and 3d).

Results

Conclusion