کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2186113 | 1096035 | 2009 | 14 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Sox9 Represses α-Sarcoglycan Gene Expression in Early Myogenic Differentiation Sox9 Represses α-Sarcoglycan Gene Expression in Early Myogenic Differentiation](/preview/png/2186113.png)
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.
Journal: Journal of Molecular Biology - Volume 394, Issue 1, 20 November 2009, Pages 1–14