438 DNA methylation patterns and transcriptional regulation during pig fetal skeletal muscle development

IF 2.7 2区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Journal of animal science Pub Date : 2024-09-14 DOI:10.1093/jas/skae234.119
Catherine W Ernst
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Abstract

Fetal development is controlled by a complex cascade of highly regulated and coordinated gene expression patterns. Epigenetic mechanisms have important roles in regulating development and differentiation. Among such mechanisms, DNA methylation exhibits context-specific associations with gene expression and has been shown to be highly dynamic during developmental processes. We performed whole-genome bisulfite sequencing (WGBS) to assess DNA methylation in pig longissimus dorsi muscle at 41- and 70-d 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 vs. 41 dg. Developmental DMRs exhibited feature-specific enrichment in gene regulatory regions, as well as in regions proximal to micro-RNAs (miRNAs) that have known roles in myogenesis. Integration of methylation and transcriptomic data revealed strong associations between differential gene methylation and transcript abundance. We surveyed myogenic regulatory factor (MRF) genes to determine if differential methylation was present in expected genomic regions. Within the MYF5 and MYF6 locus, MYF5 was significantly promoter-hypermethylated at 70 dg, whereas MYF6 was significantly hypomethylated upstream of its transcription start site. MYF5 is the earliest MRF to be expressed and primarily functions in myoblast proliferation and determination, while MYF6 functions in muscle cell differentiation. Thus, these patterns were consistent with expected downregulation of MYF5 and upregulation of MYF6 as muscle development progresses and demonstrate that differential methylation is evident at myogenic transcription factors. 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 also show that developmental DMRs are enriched for GWAS SNPs associated with muscle physiology and meat quality traits, demonstrating the potential for epigenetic processes to influence phenotypic diversity. Our results enhance understanding of DNA methylation dynamics in pig fetal skeletal muscle and reveal putative cis-regulatory elements governed by epigenetic processes during porcine myogenesis.
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438 猪胎儿骨骼肌发育过程中的 DNA 甲基化模式和转录调控
胎儿的发育是由一连串高度调控和协调的复杂基因表达模式控制的。表观遗传机制在调节发育和分化方面发挥着重要作用。在这些机制中,DNA 甲基化与基因表达有特定的关联,并已被证明在发育过程中具有高度动态性。我们进行了全基因组亚硫酸氢盐测序(WGBS),以评估猪背长肌在妊娠41和70 dg时的DNA甲基化情况,并进行了RNA和小RNA测序,以确定甲基化和表达在肌形成阶段之间的协调变化。我们发现了45739个不同阶段的差异甲基化区域(DMRs),其中大多数(n = 34232)在70 dg与41 dg时甲基化水平较低。发育阶段的 DMRs 在基因调控区域以及已知在肌肉生成中发挥作用的微 RNA(miRNA)邻近区域表现出特异性富集。整合甲基化和转录组数据后发现,不同的基因甲基化和转录本丰度之间存在密切联系。我们调查了成肌调节因子(MRF)基因,以确定在预期的基因组区域是否存在差异甲基化。在MYF5和MYF6基因座中,MYF5在70 dg时启动子甲基化显著过高,而MYF6在其转录起始位点上游甲基化显著过低。MYF5是最早表达的MRF,主要在肌母细胞增殖和决定中发挥作用,而MYF6则在肌肉细胞分化中发挥作用。因此,这些模式与肌肉发育过程中 MYF5 的预期下调和 MYF6 的预期上调是一致的,并证明了在成肌转录因子上存在明显的甲基化差异。miRNA甲基化差异与丰度呈显著负相关,且检测的miRNA在出生后持续动态表达。基元分析表明,在低甲基化区域中,肌源性调控因子基元明显富集,这表明DNA低甲基化可能会增加肌肉特异性转录因子的可及性。我们还发现,发育DMRs富集了与肌肉生理和肉质性状相关的GWAS SNPs,这表明表观遗传过程有可能影响表型的多样性。我们的研究结果加深了人们对猪胎儿骨骼肌 DNA 甲基化动态的了解,并揭示了猪肌肉发生过程中受表观遗传过程调控的顺式调控元件。
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来源期刊
Journal of animal science
Journal of animal science 农林科学-奶制品与动物科学
CiteScore
4.80
自引率
12.10%
发文量
1589
审稿时长
3 months
期刊介绍: The Journal of Animal Science (JAS) is the premier journal for animal science and serves as the leading source of new knowledge and perspective in this area. JAS publishes more than 500 fully reviewed research articles, invited reviews, technical notes, and letters to the editor each year. Articles published in JAS encompass a broad range of research topics in animal production and fundamental aspects of genetics, nutrition, physiology, and preparation and utilization of animal products. Articles typically report research with beef cattle, companion animals, goats, horses, pigs, and sheep; however, studies involving other farm animals, aquatic and wildlife species, and laboratory animal species that address fundamental questions related to livestock and companion animal biology will be considered for publication.
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