TY - JOUR
T1 - Sox9 Represses α-Sarcoglycan Gene Expression in Early Myogenic Differentiation
AU - Hernández-Hernández, J. Manuel
AU - Delgado-Olguín, Paul
AU - Aguillón-Huerta, Verónica
AU - Furlan-Magaril, Mayra
AU - Recillas-Targa, Félix
AU - Coral-Vázquez, Ramón M.
N1 - Funding Information:
R.C.-V. was supported by grants from the Association Française contre les Myopathies (MNM 2005, Groupe A) and Instituto Mexicano del Seguro Social grant 2005/1/I/197. F.R.-T. was supported by Dirección General de Asuntos del Personal Académico-UNAM (IN214407) and Consejo Nacional de Ciencia y Tecnología (CONACyT) through grants 42653-Q and 58767. J.M.H.-H. was supported by CONACyT (189007) and by the Instituto Mexicano del Seguro Social Fellowships awards. M.F.-M. is a fellowship recipient from CONACyT (170087).
PY - 2009/11/20
Y1 - 2009/11/20
N2 - Alpha sarcoglycan (α-SG) is highly expressed in differentiated striated muscle, and its disruption causes limb-girdle muscular dystrophy. Accordingly, the myogenic master regulator MyoD finely modulates its expression. However, the mechanisms preventing α-SG gene expression at early stages of myogenic differentiation remain unknown. In this study, we uncovered Sox9, which was not previously known to directly bind muscle gene promoters, as a negative regulator of α-SG gene expression. Reporter gene and chromatin immunoprecipitation assays revealed three functional Sox-binding sites that mediate α-SG promoter activity repression during early myogenic differentiation. In addition, we show that Sox9-mediated inhibition of α-SG gene expression is independent of MyoD. Moreover, we provide evidence suggesting that Smad3 enhances the repressive activity of Sox9 over α-SG gene expression in a transforming growth factor-β-dependent manner. On the basis of these results, we propose that Sox9 and Smad3 are responsible for preventing precocious activation of α-SG gene expression during myogenic differentiation.
AB - Alpha sarcoglycan (α-SG) is highly expressed in differentiated striated muscle, and its disruption causes limb-girdle muscular dystrophy. Accordingly, the myogenic master regulator MyoD finely modulates its expression. However, the mechanisms preventing α-SG gene expression at early stages of myogenic differentiation remain unknown. In this study, we uncovered Sox9, which was not previously known to directly bind muscle gene promoters, as a negative regulator of α-SG gene expression. Reporter gene and chromatin immunoprecipitation assays revealed three functional Sox-binding sites that mediate α-SG promoter activity repression during early myogenic differentiation. In addition, we show that Sox9-mediated inhibition of α-SG gene expression is independent of MyoD. Moreover, we provide evidence suggesting that Smad3 enhances the repressive activity of Sox9 over α-SG gene expression in a transforming growth factor-β-dependent manner. On the basis of these results, we propose that Sox9 and Smad3 are responsible for preventing precocious activation of α-SG gene expression during myogenic differentiation.
KW - Smad3
KW - Sox9
KW - alpha sarcoglycan promoter
KW - dystrophy
KW - skeletal muscle
UR - http://www.scopus.com/inward/record.url?scp=70350135732&partnerID=8YFLogxK
U2 - 10.1016/j.jmb.2009.08.057
DO - 10.1016/j.jmb.2009.08.057
M3 - Artículo
C2 - 19729026
SN - 0022-2836
VL - 394
SP - 1
EP - 14
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 1
ER -