State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
DNA Res. 2021 May 2;28(2). doi: 10.1093/dnares/dsab003.
Myofibres (primary and secondary myofibre) are the basic structure of muscle and the determinant of muscle mass. To explore the skeletal muscle developmental processes from primary myofibres to secondary myofibres in pigs, we conducted an integrative three-dimensional structure of genome and transcriptomic characterization of longissimus dorsi muscle of pig from primary myofibre formation stage [embryonic Day 35 (E35)] to secondary myofibre formation stage (E80). In the hierarchical genomic structure, we found that 11.43% of genome switched compartment A/B status, 14.53% of topologically associating domains are changed intradomain interactions (D-scores) and 2,730 genes with differential promoter-enhancer interactions and (or) enhancer activity from E35 to E80. The alterations of genome architecture were found to correlate with expression of genes that play significant roles in neuromuscular junction, embryonic morphogenesis, skeletal muscle development or metabolism, typically, NEFL, MuSK, SLN, Mef2D and GCK. Significantly, Sox6 and MATN2 play important roles in the process of primary to secondary myofibres formation and increase the regulatory potential score and genes expression in it. In brief, we reveal the genomic reorganization from E35 to E80 and construct genome-wide high-resolution interaction maps that provide a resource for studying long-range control of gene expression from E35 to E80.
肌纤维(初级和次级肌纤维)是肌肉的基本结构,也是肌肉质量的决定因素。为了探索猪从初级肌纤维到次级肌纤维的骨骼肌发育过程,我们对猪背最长肌从初级肌纤维形成阶段(胚胎第 35 天[E35])到次级肌纤维形成阶段(E80)进行了基因组和转录组的综合三维结构特征分析。在层次基因组结构中,我们发现 11.43%的基因组切换了隔室 A/B 状态,14.53%的拓扑关联域改变了域内相互作用(D 分数),2730 个基因的启动子-增强子相互作用和(或)增强子活性发生了变化,从 E35 到 E80。基因组结构的改变与在神经肌肉接头、胚胎形态发生、骨骼肌发育或代谢中发挥重要作用的基因表达相关,这些基因通常包括 NEFL、MuSK、SLN、Mef2D 和 GCK。值得注意的是,Sox6 和 MATN2 在从初级肌纤维到次级肌纤维形成的过程中发挥着重要作用,增加了其调控潜力评分和基因表达。总之,我们揭示了从 E35 到 E80 的基因组重排,并构建了全基因组高分辨率相互作用图谱,为研究从 E35 到 E80 的长距离基因表达调控提供了资源。