The development of skeletal muscle are complicated processes involving genes responsible for proper muscle morphology, contractility, cell proliferation, differentiation, interactions, migration, and death. The three-dimensional chromatin architecture of skeletal muscle development has not been studied intensively although dynamic transcriptional regulation during differentiation of muscle cells is one of the most deeply studied processes. The RNA-seq was used to analyze the transcriptome pattern during chicken muscle development across 12 stages. Hi-C was used to build a chromatin architectures during four representative stages. ChIP-seq was conducted to identify enhancers in these four stages, which are occupied by histone H3K27ac and H3K4me3 peaks. Results show that large-scale genome architecture changes are mostly unidirectional, and coupled by complex on/off dynamic patterns of gene expression. Specifically, we observed 258.30 Mb of the genome undergoing A/B compartment switching. Notable alterations (316.57 Mb) of interaction frequencies within TADs were observed. Substantial aging-associated genes exhibited ascending connectivity with the compartment transition from repressive to active status during muscle development. Some muscle-related gene promoters that interacted with active enhancers during development, and some myopathy/aging-associated genes that were activated in aging muscle were founded. These results provide key insights into skeletal muscle development in vivo, and offer a valuable resource that allows in-depth functional characterization of candidate genes.

中文翻译：

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鸡骨骼肌发育过程中的 3D 基因组变化1

骨骼肌的发育是一个复杂的过程，涉及负责适当肌肉形态、收缩性、细胞增殖、分化、相互作用、迁移和死亡的基因。尽管肌肉细胞分化过程中的动态转录调控是研究最深入的过程之一，但骨骼肌发育的三维染色质结构尚未得到深入研究。 RNA-seq 用于分析鸡肌肉发育过程中 12 个阶段的转录组模式。 Hi-C 用于在四个代表性阶段构建染色质结构。进行 ChIP-seq 来鉴定这四个阶段的增强子，这些增强子被组蛋白 H3K27ac 和 H3K4me3 峰占据。结果表明，大规模的基因组结构变化大多是单向的，并且与基因表达的复杂开/关动态模式耦合。具体来说，我们观察到 258.30 Mb 的基因组正在进行 A/B 区室转换。观察到 TAD 内相互作用频率的显着变化 (316.57 Mb)。在肌肉发育过程中，与衰老相关的基因随着区室从抑制状态转变为活跃状态而表现出上升的连通性。发现了一些在发育过程中与活性增强子相互作用的肌肉相关基因启动子，以及一些在衰老肌肉中被激活的肌病/衰老相关基因。这些结果提供了对体内骨骼肌发育的重要见解，并提供了宝贵的资源，可以对候选基因进行深入的功能表征。