Transcription cofactor Vgl-2 is required for skeletal muscle differentiation

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 C(2)C(12) 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.