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 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.
Cardiovascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Hsiao-Huei
HH
Chen
Tomoji
T
Maeda
Steven J
SJ
Mullett
Alexandre F R
AF
Stewart
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D018274:Electroporation; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D051379:Mice / Q000196:embryology / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000196:embryology* / Q000378:metabolism; D009841:Oligonucleotides; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D009841:Oligonucleotides; D000091262:TEA Domain Transcription Factors; C083215:Tead1 protein, mouse; D014157:Transcription Factors; C483778:Vgll2 protein, mouse