Abstract
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. genesis 39:273–279, 2004. © 2004 Wiley‐Liss, Inc.