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J. Biol. Chem., Vol. 277, Issue 50, 48889-48898, December 13, 2002
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From the 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 10T1/2 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.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AY056583 and AF542181.
Mammalian Vestigial-like 2, a Cofactor of TEF-1 and
MEF2 Transcription Factors That Promotes Skeletal Muscle
Differentiation*
,¶
Cardiovascular Institute, School of
Medicine, and § Department of Biological Sciences,
University of Pittsburgh, Pennsylvania 15213
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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