Bioscience Methods 2025, Vol.16, No.2, 83-99 http://bioscipublisher.com/index.php/bm 90 also showed abnormal methylation (Zhou et al., 2022). These changes are associated with impaired muscle fiber development, indicating that external factors such as nutrition can affect goat muscle development through epigenetic pathways. The authors further pointed out that methylation in the promoter regions of genes such as MYF5 and MYOD is closely related to muscle growth and development, and its changes may mediate the developmental programming effects of nutritional stress on muscle. The overall dynamics of DNA methylation are also important during normal development. High-throughput methylation sequencing (WGBS) has been used to analyze methylome changes in livestock skeletal muscle development. Ren et al. (2023) performed WGBS comparisons on the skeletal muscles of Hainan black goats and their hybrid offspring and found that the methylation distribution of the two strains was generally consistent across the genome, but there was differential methylation in specific gene regions, and these differences were associated with muscle growth performance. They identified thousands of differentially methylated regions (DMRs) and the genes involved, and combined RNA-seq to find 189 differentially expressed genes (DEGs), and finally locked in 11 hub genes that were both differentially methylated and differentially expressed. Among them, 9 genes were significantly associated with muscle growth traits (eye muscle area, muscle height and weight, etc.). In particular, the methylation and expression of the PRKG1 gene were negatively correlated with muscle growth traits, that is, muscle growth slowed down when the methylation level increased and the expression decreased. In contrast, some FOX family transcription factors such as FOXO3 and FOXO6 have lower promoter methylation and higher expression in high growth performance groups, which help protect muscle fibers from stress and promote myotube differentiation. The study concluded that diverse DNA methylation modifications jointly maintain glycogen storage around muscle fibers by affecting key genes, thereby supporting the growth of muscle fibers. It can be seen that in livestock such as goats, differences in the methylation profile of the skeletal muscle genome under different strains or different developmental conditions will lead to differences in muscle growth phenotypes. This provides us with possible epigenetic markers for evaluating and improving the production performance of meat goats. In addition to gene promoters, the pattern of DNA methylation in enhancers and other regulatory elements is also worthy of attention. The methylation of enhancers is usually negatively correlated with their activity. For example, in the study of sheep, some scholars found that some enhancer regions in muscle tissue are in a low methylation state, which is conducive to improving the expression of nearby genes and tissue function. If methylation data is combined with chromatin accessibility and gene expression through multi-omics integration, it is possible to locate those regions where changes in methylation status have the greatest impact on gene regulation. In the study of skeletal muscle development in Hu sheep, researchers found that those genomic regions that are both highly open and low in methylation are often combined with important transcription factors for muscle development, suggesting that the synergistic effect of DNA demethylation and chromatin opening promotes the activation of specific genes (such as MyoG, etc.). DNA methylation does not occur in isolation, but together with other epigenetic marks, it shapes the transcriptional program. 4.3 Epigenetic regulation of key muscle genes By linking transcription and epigenetics, we can see specifically how several key muscle genes are regulated by epigenetic mechanisms. First, take the myogenic regulatory factor MyoD as an example: MyoD is one of the master switch genes that initiate myogenic differentiation, and the methylation state and histone modification of its promoter region directly affect its expression. In undifferentiated myogenic precursor cells, the MyoD promoter may be in a partially methylated state, accompanied by inhibitory histone marks, thus maintaining a silent state. Once the cells receive differentiation signals (such as reduced FGF signals), the activity of DNA methyltransferases decreases or TET protein-mediated demethylation increases, causing the MyoD promoter CpG site to be demethylated; at the same time, inhibitory modifications such as H3K27me3 decrease, and activating modifications such as H3K27ac increase, and the MyoD gene begins to transcribe, driving the cells into the differentiation program (Zhou et al., 2023). This epigenetic switch ensures that MyoD is expressed at the appropriate time and in the appropriate cell type.
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