Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, China.
Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction of the Ministry of Education, Huazhong Agricultural University, Wuhan, China.
Nucleic Acids Res. 2022 Oct 14;50(18):10733-10755. doi: 10.1093/nar/gkac854.
Long noncoding RNAs (lncRNAs) play important roles in the spatial and temporal regulation of muscle development and regeneration. Nevertheless, the determination of their biological functions and mechanisms underlying muscle regeneration remains challenging. Here, we identified a lncRNA named lncMREF (lncRNA muscle regeneration enhancement factor) as a conserved positive regulator of muscle regeneration among mice, pigs and humans. Functional studies demonstrated that lncMREF, which is mainly expressed in differentiated muscle satellite cells, promotes myogenic differentiation and muscle regeneration. Mechanistically, lncMREF interacts with Smarca5 to promote chromatin accessibility when muscle satellite cells are activated and start to differentiate, thereby facilitating genomic binding of p300/CBP/H3K27ac to upregulate the expression of myogenic regulators, such as MyoD and cell differentiation. Our results unravel a novel temporal-specific epigenetic regulation during muscle regeneration and reveal that lncMREF/Smarca5-mediated epigenetic programming is responsible for muscle cell differentiation, which provides new insights into the regulatory mechanism of muscle regeneration.
长链非编码 RNA（lncRNAs）在肌肉发育和再生的时空调节中发挥重要作用。然而，确定它们在肌肉再生中的生物学功能和机制仍然具有挑战性。在这里，我们鉴定了一个 lncRNA 命名为 lncMREF（lncRNA 肌肉再生增强因子），它是小鼠、猪和人类中肌肉再生的保守正调控因子。功能研究表明，lncMREF 主要在分化的肌肉卫星细胞中表达，可促进成肌分化和肌肉再生。机制上，lncMREF 在肌肉卫星细胞激活并开始分化时与 Smarca5 相互作用，促进染色质可及性，从而促进 p300/CBP/H3K27ac 与肌生成调节因子（如 MyoD 和细胞分化）的基因组结合，上调其表达。我们的研究结果揭示了肌肉再生过程中的一种新的、特定于时间的表观遗传调控，并表明 lncMREF/Smarca5 介导的表观遗传编程负责肌肉细胞的分化，这为肌肉再生的调控机制提供了新的见解。
