Pig fetal skeletal muscle development is associated with genome-wide DNA hypomethylation and corresponding alterations in transcript and microRNA expression

Abstract

Fetal myogenesis represents a critical period of porcine skeletal muscle development and requires coordinated expression of thousands of genes. Epigenetic mechanisms, including DNA methylation, drive transcriptional regulation during development; however, these processes are understudied in developing porcine tissues. We performed bisulfite sequencing to assess DNA methylation in pig longissimus dorsi muscle at 41- and 70-days gestation (dg), as well as RNA- and small RNA-sequencing to identify coordinated changes in methylation and expression between myogenic stages. We identified 45 739 differentially methylated regions (DMRs) between stages, and the majority ( N = 34 232) were hypomethylated at 70 versus 41 dg. Integration of methylation and transcriptomic data revealed strong associations between differential gene methylation and expression. Differential miRNA methylation was significantly negatively correlated with abundance, and dynamic expression of assayed miRNAs persisted postnatally. Motif analysis revealed significant enrichment of myogenic regulatory factor motifs among hypomethylated regions, suggesting that DNA hypomethylation may function to increase accessibility of muscle-specific transcription factors. We show that developmental DMRs are enriched for GWAS SNPs for muscle- and meat-related traits, demonstrating the potential for epigenetic processes to influence phenotypic diversity. Our results enhance understanding of DNA methylation dynamics of porcine myogenesis and reveal putative cis-regulatory elements governed by epigenetic processes.

Integrated analysis of the DNA methylome and RNA transcriptome during the development of skeletal muscle in Duroc pigs

“…This method is now widely used in DNA methylation studies in pigs because it is a high throughput, high specificity, high sensitivity, high resolution, and high coverage technique. Corbett RJ et al used WGBS, RNA-seq, and smRNA-seq methods to identify DMRs at the stage of porcine foetal myogenesis and to validate their relationship with differentially expressed mRNAs and miRNAs [ 20 ]. In addition, a study mapped the DNA methylome in the developing pig testis via WGBS [ 21 ].…”

An Analysis of a Transposable Element Expression Atlas during 27 Developmental Stages in Porcine Skeletal Muscle: Unveiling Molecular Insights into Pork Production Traits

“…To meet this need, recent breakthroughs in multi-omics technology have been extensively exploited in pig samples. Studies have examined the dynamic alterations in DNA methylation patterns [16,17], fluctuations in mRNA or noncoding RNA expression profiles [18][19][20], dynamic changes in chromatin accessibility [21,22], alterations in the three-dimensional structure of the genome [23], and changes in the histone modifications associated with diverse cis-regulatory elements [24]. Undoubtedly, they have markedly advanced our comprehension of the genetic regulatory mechanisms governing the development of pig skeletal muscles.…”