Genome-Wide DNA Methylation Sequencing Identifies Methylation-Associated Genes Related to Porcine Skeletal Muscle Fiber Diversity
- 1Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- 2College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
- 3Institute of Animal Science & Veterinary Medicine, Hainan Academy of Agricultural Sciences, Haikou 571100, China
Abstract
Alterations in skeletal muscle fibers are closely linked to human diseases, yet the mechanisms by which DNA methylation drives muscle fiber diversity remain unclear. Here, we performed whole-genome bisulfite sequencing (WGBS) to generate single-base-resolution DNA methylomes of fast-twitch Biceps Femoris (Bf) and slow-twitch Soleus (Sol) muscles and integrated transcriptomes to reveal associations between DNA methylation and gene expression. The global methylation level in skeletal muscle averaged 4.22%, with context-specific rates of 70.0% (CG), 1.16% (CHG), and 1.12% (CHH). The distribution of methylation levels of the mCs in CG and CHG contexts was similar but distinct from that in the CHH context. Furthermore, 152,286 DMCs and 51,079 DMRs were identified between Bf and Sol muscles. Bf showed higher global methylation (4.54%) than Sol (3.90%), and distinct differences in DNA methylation occurred throughout the genomic regions and gene functional element regions. CG-context DMCs and DMRs were mainly located in CpG islands and introns, while CHG and CHH DMCs and DMRs were exon-enriched. DMR-associated genes were significantly enriched in pathways related to muscle growth and remodeling and disease-related pathways. Moreover, five DMR-linked differentially expressed genes—HSPB6, ATP2A2, TNNI1, HOXA11, and PTPN3—were identified as critical candidate regulators of muscle fiber diversity. In addition, a context-dependent (CG, CHG, CHH) relationship between DNA methylation patterns and gene expression was observed across different genomic regions in the two muscle types. Our findings highlight the essential role of DNA methylation in skeletal muscle fiber diversity and identify potential epigenetic targets and pathways.
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BibTeX
@article{zha2026genomewide,
title = {{Genome-Wide DNA Methylation Sequencing Identifies Methylation-Associated Genes Related to Porcine Skeletal Muscle Fiber Diversity}},
author = {Chengwan Zha and Bojiang Li and Wen Yang and Liming Hou and Zhe Chao and Wangjun Wu},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209093},
url = {https://www.mdpi.com/1422-0067/27/20/9093},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Genome-Wide DNA Methylation Sequencing Identifies Methylation-Associated Genes Related to Porcine Skeletal Muscle Fiber Diversity
AU - Chengwan Zha
AU - Bojiang Li
AU - Wen Yang
AU - Liming Hou
AU - Zhe Chao
AU - Wangjun Wu
PY - 2026
DA - 2026/10/14
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209093
UR - https://www.mdpi.com/1422-0067/27/20/9093
AB - Alterations in skeletal muscle fibers are closely linked to human diseases, yet the mechanisms by which DNA methylation drives muscle fiber diversity remain unclear. Here, we performed whole-genome bisulfite sequencing (WGBS) to generate single-base-resolution DNA methylomes of fast-twitch Biceps Femoris (Bf) and slow-twitch Soleus (Sol) muscles and integrated transcriptomes to reveal associations between DNA methylation and gene expression. The global methylation level in skeletal muscle averaged 4.22%, with context-specific rates of 70.0% (CG), 1.16% (CHG), and 1.12% (CHH). The distribution of methylation levels of the mCs in CG and CHG contexts was similar but distinct from that in the CHH context. Furthermore, 152,286 DMCs and 51,079 DMRs were identified between Bf and Sol muscles. Bf showed higher global methylation (4.54%) than Sol (3.90%), and distinct differences in DNA methylation occurred throughout the genomic regions and gene functional element regions. CG-context DMCs and DMRs were mainly located in CpG islands and introns, while CHG and CHH DMCs and DMRs were exon-enriched. DMR-associated genes were significantly enriched in pathways related to muscle growth and remodeling and disease-related pathways. Moreover, five DMR-linked differentially expressed genes—HSPB6, ATP2A2, TNNI1, HOXA11, and PTPN3—were identified as critical candidate regulators of muscle fiber diversity. In addition, a context-dependent (CG, CHG, CHH) relationship between DNA methylation patterns and gene expression was observed across different genomic regions in the two muscle types. Our findings highlight the essential role of DNA methylation in skeletal muscle fiber diversity and identify potential epigenetic targets and pathways.
SN - 1422-0067
ER -