Large Maf transcription factor family is a major regulator of fast type IIb myofiber determination
Large Maf transcription factor family is a major regulator of fast type IIb myofiber determination
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大 Maf 转录因子家族是快速 IIb 型肌纤维测定的主要调节因子
DOI：
10.1016/j.celrep.2023.112289
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发表时间：
2023
期刊：
影响因子：
8.8
通讯作者：
Takahashi Satoru
中科院分区：
文献类型：
--
作者：
Sadaki Shunya;Fujita Ryo;Hayashi Takuto;Nakamura Ayano;Okamura Yui;Fuseya Sayaka;Hamada Michito;Warabi Eiji;Kuno Akihiro;Ishii Akiko;Muratani Masafumi;Okada Risa;Shiba Dai;Kudo Takashi;Takeda Shin’ichi;Takahashi Satoru
肌纤维被广泛地表征为抗疲劳慢缩（I型）纤维和快速疲劳快缩（IIa/IIx/IIb型）纤维。然而，肌纤维类型的分子调控并不完全清楚，特别是，关于快缩肌的调节因子的信息很少。在这里，我们证明了大Maf转录因子家族决定快速IIb型肌纤维规格在小鼠中。值得注意的是，三个大Maf的消融导致IIb型肌纤维的急剧损失，导致耐力增强和肌肉力量减少。相反，I型比目鱼肌中每个大Maf的过表达诱导IIb型肌纤维。在机制上，大Maf直接结合肌球蛋白重链4启动子上的Maf识别元件，其编码IIb型肌球蛋白重链，驱动其表达。这项工作确定了大Maf转录因子家族作为快速IIb型肌肉测定的主要调节因子。
Myofibers are broadly characterized as fatigue-resistant slow-twitch (type I) fibers and rapidly fatiguing fast-twitch (type IIa/IIx/IIb) fibers. However, the molecular regulation of myofiber type is not entirely understood; particularly, information on regulators of fast-twitch muscle is scarce. Here, we demonstrate that the large Maf transcription factor family dictates fast type IIb myofiber specification in mice. Remarkably, the ablation of three large Mafs leads to the drastic loss of type IIb myofibers, resulting in enhanced endurance capacity and the reduction of muscle force. Conversely, the overexpression of each large Maf in the type I soleus muscle induces type IIb myofibers. Mechanistically, a large Maf directly binds to the Maf recognition element on the promoter of myosin heavy chain 4,which encodes the type IIb myosin heavy chain, driving its expression. This work identifies the large Maf transcription factor family as a major regulator for fast type IIb muscle determination.