The dystrophin promoter is negatively regulated by YY1 in undifferentiated muscle cells
The dystrophin promoter is negatively regulated by YY1 in undifferentiated muscle cells
复制标题
DOI：
10.1074/jbc.273.50.33708
复制
发表时间：
1998-12-11
影响因子：
4.8
通讯作者：
Oliviero, S
中科院分区：
文献类型：
--
作者：
Galvagni, F;Cartocci, E;Oliviero, S
肌营养不良蛋白基因转录在肌细胞分化过程中上调。它在肌肉细胞中的表达是通过正调节血清反应因子和肌营养不良蛋白启动子弯曲因子 (DPBF) 与启动子上存在的调节 CArG 元件的结合来诱导的。在这里，我们表明肌营养不良蛋白 CArG 盒也被锌指核因子 YY1 识别。瞬时转染实验表明，YY1 负向调节 C2C12 肌细胞中肌营养不良蛋白的转录。在肌营养不良蛋白 CArG 上，YY1 元件与结构因子 DPBF 竞争。我们进一步表明，YY1 和 DPBF 与 CArG 元件的结合诱导相反的 DNA 弯曲，表明它们的结合诱导替代的启动子结构。随着 C2C12 肌管形成，YY1 减少，我们观察到 YY1（而非 DPBF）是 m-钙蛋白酶的底物，m-钙蛋白酶是一种在肌细胞分化中上调的蛋白酶。因此，非分化肌细胞中高水平的 YY1 至少部分通过干扰启动子的空间组织来下调肌营养不良蛋白启动子。
The dystrophin gene transcription is up-regulated during muscle cell differentiation. Its expression in muscle cells is induced by the binding of the positive regulators serum response factor and dystrophin promoter bending factor (DPBF) on a regulatory CArG element present on the promoter. Here we show that the dystrophin CArG box is also recognized by the zinc finger nuclear factor YY1. Transient transfection experiments show that YY1 negatively regulates dystrophin transcription in C2C12 muscle cells. On the dystrophin CArG element YY1 competes with the structural factor DPBF. We further show that YY1 and DPBF binding to the CArG element induce opposite DNA bends suggesting that their binding induces alternative promoter structures. Along with C2C12 myotube formation YY1 is reduced and we observed that YY1, but not DPBF, is a substrate of m-calpain, a protease that is up-regulated in muscle cell differentiation. Thus, high levels of YY1 in non-differentiated muscle cells down-regulate the dystrophin promoter, at least in part, by interfering with the spatial organization of the promoter.