| Abstract | Alpha sarcoglycan (alpha-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 alpha-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 alpha-SG gene expression. Reporter gene and chromatin immunoprecipitation assays revealed three functional Sox-binding sites that mediate alpha-SG promoter activity repression during early myogenic differentiation. In addition, we show that Sox9-mediated inhibition of alpha-SG gene expression is independent of MyoD. Moreover, we provide evidence suggesting that Smad3 enhances the repressive activity of Sox9 over alpha-SG gene expression in a transforming growth factor-beta-dependent manner. On the basis of these results, we propose that Sox9 and Smad3 are responsible for preventing precocious activation of alpha-SG gene expression during myogenic differentiation. |
| Authors | J Manuel Hernández-Hernández, Paul Delgado-Olguín, Verónica Aguillón-Huerta, Mayra Furlan-Magaril, Félix Recillas-Targa, Ramón M Coral-Vázquez
(Affiliation: Unidad de Investigación Médica en Genética Humana, Hospital de Pediatría, Centro Médico Nacional Siglo XXI-IMSS, México, D.F., México.)
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| Journal | Journal of molecular biology
(J Mol Biol)
Vol. 394
Issue 1
Pg. 1-14
(Nov 20 2009)
ISSN: 1089-8638 [Electronic] England |
| PMID | 19729026
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- MyoD Protein
- Repressor Proteins
- SOX9 Transcription Factor
- Sarcoglycans
- Smad3 Protein
- Sox9 protein, mouse
- Transforming Growth Factor beta
|
| Topics |
- Animals
- Base Sequence
- Binding Sites
- Cell Differentiation
(drug effects, genetics)
- Gene Expression Regulation
(drug effects)
- Mice
- Models, Genetic
- Molecular Sequence Data
- Muscle Development
(drug effects, genetics)
- MyoD Protein
(metabolism)
- Myoblasts
(cytology, drug effects, metabolism)
- Phosphorylation
(drug effects)
- Promoter Regions, Genetic
(genetics)
- Protein Binding
(drug effects)
- Repressor Proteins
(metabolism)
- SOX9 Transcription Factor
(metabolism)
- Sarcoglycans
(genetics, metabolism)
- Smad3 Protein
(metabolism)
- Transcription, Genetic
(drug effects)
- Transforming Growth Factor beta
(pharmacology)
|
