Zinc finger protein 422 (Zfp422) is a widely expressed zinc finger protein that serves as a transcriptional factor to regulate downstream gene expression, but until now, little is known about its roles in myogenesis. We found here that Zfp422 plays a critical role in skeletal muscle development and regeneration. It highly expresses in mouse skeletal muscle during embryonic development. Specific knockout of Zfp422 in skeletal muscle impaired embryonic muscle formation. Satellite cell-specific Zfp422 deletion severely inhibited muscle regeneration. Myoblast differentiation and myotube formation were suppressed in Zfp422-deleted C2C12 cells, isolated primary myoblasts, and satellite cells. Chromatin Immunoprecipitation Sequencing (ChIP-Seq) revealed that Zfp422 regulated ephrin type-A receptor 7 (EphA7) expression by binding an upstream 169-bp DNA sequence, which was proved to be an enhancer of EphA7. Knocking EphA7 down in C2C12 cells or deleting Zfp422 in myoblasts will inhibit cell apoptosis which is required for myoblast differentiation. These results indicate that Zfp422 is essential for skeletal muscle differentiation and fusion, through regulating EphA7 expression to maintain proper apoptosis.

中文翻译：

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Zfp422 通过调节 EphA7 诱导适当的成肌细胞凋亡来促进骨骼肌分化。

锌指蛋白 422 (Zfp422) 是一种广泛表达的锌指蛋白，可作为调节下游基因表达的转录因子，但直到现在，对其在肌生成中的作用知之甚少。我们在这里发现 Zfp422 在骨骼肌发育和再生中起着关键作用。它在胚胎发育过程中在小鼠骨骼肌中高度表达。骨骼肌中 Z​​fp422 的特异性敲除会损害胚胎肌肉的形成。卫星细胞特异性 Zfp422 缺失严重抑制肌肉再生。在 Zfp422 缺失的 C2C12 细胞、分离的原代成肌细胞和卫星细胞中，成肌细胞分化和肌管形成受到抑制。染色质免疫沉淀测序 (ChIP-Seq) 显示 Zfp422 通过结合上游 169 bp DNA 序列来调节 ephrin A 型受体 7 (EphA7) 的表达，该序列被证明是 EphA7 的增强子。敲低 C2C12 细胞中的 EphA7 或删除成肌细胞中的 Zfp422 将抑制成肌细胞分化所需的细胞凋亡。这些结果表明 Zfp422 通过调节 EphA7 表达来维持适当的细胞凋亡，对骨骼肌分化和融合至关重要。