Integrated Analysis of DNA Methylome and Transcriptome Reveals Regulatory Mechanism in the Longissimus Dorsi of Duroc Pigs
DNA methylation plays a pivotal role in the epigenetic regulation of gene expression and holds promise for enhancing livestock meat production. In this study, we analyzed the DNA methylome and transcriptome of the longissimus dorsi muscle (LDM) in Duroc pigs with varying growth rates. Our results re...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
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| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/11/786 |
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| Summary: | DNA methylation plays a pivotal role in the epigenetic regulation of gene expression and holds promise for enhancing livestock meat production. In this study, we analyzed the DNA methylome and transcriptome of the longissimus dorsi muscle (LDM) in Duroc pigs with varying growth rates. Our results reveal that DNA methylation suppressed the expression of key muscle development markers (<i>MYOD</i>, <i>MYOG</i>, <i>MHC1</i>) and proliferation markers (<i>PI67</i>, <i>PCNA</i>), as well as the protein expression and phosphorylation of PI3K and AKT (<i>p</i> < 0.05). Dual-luciferase reporter assays and EMSA showed that SP1 overexpression enhanced the luciferase activity of the wild-type <i>LPAR1</i> promoter, an effect amplified by the demethylating agent 5-AZA (<i>p</i> < 0.05). The EMSA further demonstrates the relationship between SP1 and the <i>LPAR1</i> promoter region. Overexpression of SP1 upregulated <i>LPAR1</i> expression at both the mRNA and protein levels (<i>p</i> < 0.05). Knockdown of <i>LPAR1</i> reduced muscle marker gene expression and delayed myotube formation, while silencing <i>SP1</i> disrupted the expression of <i>LPAR1</i>, <i>MEF2C</i>, and <i>MHC1</i> (<i>p</i> < 0.05), and the demethylation induced by 5-AZA partially reversed these effects. These findings suggest that the DNA methylation/<i>SP1</i>/<i>LPAR1</i> axis is critical for skeletal muscle growth and development, underscoring the regulatory role of DNA methylation in muscle formation. |
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| ISSN: | 2073-4409 |