Transcription cofactor Vgl-2 is required for skeletal muscle differentiation
Transcription cofactor Vgl-2 is required for skeletal muscle differentiation
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DOI：
10.1002/gene.20055
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发表时间：
2004-08-01
期刊：
影响因子：
1.5
通讯作者：
Stewart, AFR
中科院分区：
文献类型：
--
作者：
Chen, HH;Maeda, T;Stewart, AFR
TEF-1转录因子调节骨骼肌中的基因表达，但不是肌肉特异性的。相反，TEF-1因子依赖于肌肉特异性辅因子Vestigial-like 2（Vgl-2），一种与果蝇退化相关的蛋白质。以前，我们发现Vgl-2促进骨骼肌分化并激活肌肉特异性启动子。然而，Vgl-2调节TEF-1因子的机制和肌肉特异性基因表达对Vgl-2的需求尚不清楚。在果蝇中，退化改变了TEF-1同源物的DNA结合特异性，以驱动翅膀和飞行肌肉特异性基因的表达。在这里，凝胶迁移率变动分析表明，Vgl-2差异影响不同TEF-1因子的DNA结合。使用反义吗啉代，我们阻断了Vgl-2和肌肉特异性基因在肌源性C2 C12细胞系和鸡胚中的表达，通过电穿孔。这些结果表明，Vgl-2是肌肉基因表达所必需的，部分是通过在肌肉分化期间转换TEF-1因子的DNA结合。(C)2004 Wiley-Liss，Inc.
TEF-1 transcription factors regulate gene expression in skeletal muscle but are not muscle-specific. Instead, TEF-1 factors rely on the muscle-specific cofactor Vestigial-like 2 (Vgl-2), a protein related to Drosophila vestigial. Previously, we showed that Vgl-2 promotes skeletal muscle differentiation and activates muscle-specific promoters. However, the mechanism whereby Vgl-2 regulates TEF-1 factors and the requirement for Vgl-2 for muscle-specific gene expression were not known. In Drosophila, vestigial alters DNA binding specificity of the TEF-1 homolog scalloped to drive wing and flight muscle-specific gene expression. Here, gel mobility shift assays show that Vgl-2 differentially affects DNA binding of different TEF-1 factors. Using an antisense morpholino, we blocked the expression of Vgl-2 and a muscle-specific gene in the myogenic C2C12 cell line and in chick embryos by electroporation. These results demonstrate that Vgl-2 is required for muscle gene expression, in part by switching DNA binding of TEF-1 factors during muscle differentiation. (C) 2004 Wiley-Liss, Inc.