A change in cis-regulatory logic underlying obligate versus facultative muscle multinucleation in chordates.
A change in cis-regulatory logic underlying obligate versus facultative muscle multinucleation in chordates.
复制标题
脊索动物中专性与兼性肌肉多核的顺式调节逻辑的变化。
DOI：
10.1101/2024.03.06.583753
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Stolfi,Alberto
中科院分区：
文献类型：
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作者：
Johnson,ChristopherJ;Zhang,Zheng;Zhang,Haifeng;Shang,Renjie;Piekarz,KatarzynaM;Bi,Pengpeng;Stolfi,Alberto
脊椎动物和被囊动物是姐妹群，它们共享一个共同的融合因子Myomaker（Mymk），该因子驱动成肌细胞融合和肌肉多核化。然而，他们在何时何地表达Mymk的问题上存在分歧。在脊椎动物中，所有发育中的骨骼肌都表达Mymk，并且是专性多核的。在被囊动物中，Mymk仅在变性后的多核肌肉中表达，但在单核幼虫肌肉中不存在。在这项研究中，我们表明，顺式调控序列的差异Mymk的启动子区域的基础上不同的时空模式，其转录激活被囊动物和脊椎动物。虽然在脊椎动物中，肌源性调节因子（MRF），如MyoD1单独需要和足够的Mymk转录在所有骨骼肌，我们表明，转录Mymk在变性后的被囊海鞘肌肉需要MRF，MyoD和早期B细胞因子（EBF）的组合活性。这种宏观进化差异似乎是编码顺式，可能是由于存在一个推定的Ebf结合位点附近的预测MRF结合位点的玻璃海鞘Mymk启动子。我们进一步讨论了如何Mymk和成肌细胞融合可能已在被囊动物和脊椎动物的最后共同祖先，我们提出了两个模型进行调节。
Vertebrates and tunicates are sister groups that share a common fusogenic factor, Myomaker (Mymk), that drives myoblast fusion and muscle multinucleation. Yet they are divergent in when and where they express Mymk. In vertebrates, all developing skeletal muscles express Mymk and are obligately multinucleated. In tunicates, Mymk is expressed only in post-metamorphic multinucleated muscles, but is absent from mononucleated larval muscles. In this study, we demonstrate that cis-regulatory sequence differences in the promoter region of Mymk underlie the different spatiotemporal patterns of its transcriptional activation in tunicates and vertebrates. Although in vertebrates myogenic regulatory factors (MRFs) such as MyoD1 alone are required and sufficient for Mymk transcription in all skeletal muscles, we show that transcription of Mymk in post-metamorphic muscles of the tunicate Ciona requires the combinatorial activity of MRF, MyoD and Early B-cell Factor (Ebf). This macroevolutionary difference appears to be encoded in cis, likely due to the presence of a putative Ebf-binding site adjacent to predicted MRF binding sites in the Ciona Mymk promoter. We further discuss how Mymk and myoblast fusion might have been regulated in the last common ancestor of tunicates and vertebrates, for which we propose two models.