title: Mammalian vestigial-like 2, a cofactor of TEF-1 and MEF2 transcription factors that promotes skeletal muscle differentiation.
abstract: Expression of many skeletal muscle-specific genes depends on TEF-1 (transcription enhancer factor-1) and MEF2 transcription factors. In Drosophila, the TEF-1 homolog Scalloped interacts with the cofactor Vestigial to drive differentiation of the wing and indirect flight muscles. Here, we identify three mammalian vestigial-like genes, Vgl-1, Vgl-2, and Vgl-3, that share homology in a TEF-1 interaction domain. Vgl-1 and Vgl-3 transcripts are enriched in the placenta, whereas Vgl-2 is expressed in the differentiating somites and branchial arches during embryogenesis and is skeletal muscle-specific in the adult. During muscle differentiation, Vgl-2 mRNA levels increase and Vgl-2 protein translocates from the cytoplasm to the nucleus. In situ hybridization revealed co-expression of Vgl-2 with myogenin in the differentiating muscle of embryonic myotomes but not in newly formed somites prior to muscle differentiation. Like Vgl-1, Vgl-2 interacts with TEF-1. In addition, we show that Vgl-2 interacts with MEF2 in a mammalian two-hybrid assay and that Vgl-2 selectively binds to MEF2 in vitro. Co-expression of Vgl-2 with MEF2 markedly co-activates an MEF2-dependent promoter through its MEF2 element. Overexpression of Vgl-2 in MyoD-transfected 10T(1/2) cells markedly increased myosin heavy chain expression, a marker of terminal muscle differentiation. These results identify Vgl-2 as an important new component of the myogenic program.
authors.affiliation: Cardiovascular Institute, School of Medicine, University of Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Tomoji
authors.initials: T
authors.lastname: Maeda
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Chapman
authors.forename: Alexandre F R
authors.initials: AF
authors.lastname: Stewart
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002454:Cell Differentiation; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D064326:MEF2 Transcription Factors; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000166:cytology*; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; D009124:Muscle Proteins; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D014157:Transcription Factors; C470573:VGLL2 protein, human