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J. Biol. Chem., Vol. 275, Issue 21, 16103-16109, May 26, 2000
From the Human Molecular Genetic Group, Cell Biology Unit, CNRS
UPR-1142, Institut de Génétique Humaine, 141 Rue de la
Cardonille, 34396 Montpellier cedex 5, France
SOX proteins belong to a multigenic family
characterized by a unique DNA binding domain, known as the high
mobility group box, that is related to that of the testis determining
gene SRY. cDNA sequences for more than 30 SOX genes have been identified, and some are known to have
diverse roles in vertebrate differentiation and development. Here, we
report the isolation and characterization of mouse Sox15
that was uncovered during a screen for high mobility group box
containing transcription factors that are expressed at different levels
during skeletal muscle differentiation. Sox15 cDNAs
were found at a much higher frequency in myoblasts prior to their
differentiation into myotubes. Electrophoretic mobility shift assays
indicated that recombinant SOX15 protein was capable of binding to a
consensus DNA binding site for SOX proteins. When overexpressed in
C2C12 myoblasts, wild type SOX15, but not a C-terminal truncated form
or the related protein SOX11, specifically inhibited activation of
muscle-specific genes and expression of the basic helix-loop-helix
myogenic factors myogenin and MyoD, resulting in a failure of the cells
to differentiate into myotubes. These results suggest a specific and
repressive role for SOX15, requiring the C-terminal domain, during myogenesis.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF182945.
Muscle Differentiation Is Antagonized by SOX15, a New Member of
the SOX Protein Family*
,
*
This work was supported by grants from the Center National
de la Recherche Scientifique and the Association pour la Recherche contre le Cancer.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.
To whom correspondence should be addressed. Tel.:
33-4-99-61-99-41; Fax: 33-4-99-61-99-01; E-mail:
beranger@igh.cnrs.fr.
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