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Article Dans Une Revue Science Advances Année : 2020

Human myotube formation is determined by MyoD-Myomixer/Myomaker axis

Junfei Wen
Jiacheng Chen
Renjie Shang
Pengpeng Bi

Résumé

Myoblast fusion is essential for formations of myofibers, the basic cellular and functional units of skeletal muscles. Recent genetic studies in mice identified two long-sought membrane proteins, Myomaker and Myomixer, which cooperatively drive myoblast fusion. It is unknown whether and how human muscles, with myofibers of tremendously larger size, use this mechanism to achieve multinucleations. Here, we report an interesting fusion model of human myoblasts where Myomaker is sufficient to induce low-grade fusion, while Myomixer boosts its efficiency to generate giant myotubes. By CRISPR mutagenesis and biochemical assays, we identified MyoD as the key molecular switch of fusion that is required and sufficient to initiate Myomixer and Myomaker expression. Mechanistically, we defined the E-box motifs on promoters of Myomixer and Myomaker by which MyoD induces their expression for multinucleations of human muscle cells. Together, our study uncovered the key molecular apparatus and the transcriptional control mechanism underlying human myoblast fusion.
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Origine : Publication financée par une institution

Dates et versions

hal-03276082 , version 1 (01-07-2021)

Identifiants

Citer

Haifeng Zhang, Junfei Wen, Anne Bigot, Jiacheng Chen, Renjie Shang, et al.. Human myotube formation is determined by MyoD-Myomixer/Myomaker axis. Science Advances , 2020, 6 (51), pp.eabc4062. ⟨10.1126/sciadv.abc4062⟩. ⟨hal-03276082⟩
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