TEAD1 controls C2C12 cell proliferation and differentiation and regulates three novel target genes.
TEAD1 controls C2C12 cell proliferation and differentiation and regulates three novel target genes.
复制标题
DOI：
10.1016/j.cellsig.2012.11.027
复制
发表时间：
2013-03
影响因子：
4.8
通讯作者：
Feng-Ling Wang;Hongyang Wang;Hao Wu;H. Qiu;Cuiping Zeng;Ling Sun;Bang Liu
中科院分区：
文献类型：
--
作者：
Feng-Ling Wang;Hongyang Wang;Hao Wu;H. Qiu;Cuiping Zeng;Ling Sun;Bang Liu
TEAD1是参与肌肉特异性基因激活的转录因子，例如心肌肌钙蛋白T基因、骨骼肌肌动蛋白、肌球蛋白重链基因。在这里，我们报道了TEAD1在不同的小鼠组织中普遍表达，并且在小鼠成肌细胞系C2C12的分化过程中上调。功能分析显示TEAD1基因的过表达可以阻滞C2C12细胞周期并促进C2C12细胞分化。为了了解TEAD1在肌肉发育中的生理作用，通过表达分析、启动子活性测量测定鉴定了TEAD1的三个新调控基因Mrpl21、Ndufa6和Ccne1。检测细胞分化过程中目的基因的表达模式。 Mrpl21和Ndufa6基因在细胞分化过程中上调，而Ccne1基因则显着下调。在C2C12中过表达Mrpl21和Ndufa6可以上调Myh4基因表达，从而促进C2C12分化，但不影响细胞周期。 Ccne1 与 Ndufa6 共过表达导致 Myh4 表达减少，S 期细胞数量略有增加。总之，我们的结果表明 TEAD1 可能通过其靶基因 Mrpl21、Ndufa6 和 Ccne1 介导肌肉发育。
TEAD1 is a transcription factor involved in activation of muscle specific genes, such as the cardiac muscle troponin T gene, skeletal muscle actin, myosin heavy chains genes. Here, we reported that TEAD1 was expressed ubiquitously in different mouse tissues and was up-regulated in differentiation process of the mouse myoblast cell line C2C12. Functional assay revealed that overexpression of TEAD1 gene can arrest the C2C12 cell cycle and promote C2C12 cell differentiation. To understand the physiological role of TEAD1 in muscle development, three new regulated genes of TEAD1, Mrpl21, Ndufa6 and Ccne1, were identified by expression analysis, promoter activity measurement assay. The expression patterns of target genes were detected in the cell differentiation process. The Mrpl21 and Ndufa6 genes were up-regulated in cell differentiation while Ccne1 gene was significantly down-regulated. Overexpression of Mrpl21 and Ndufa6 in C2C12 can up-regulate Myh4 gene expression thus promote C2C12 differentiation, but did not affect cell cycle. Co-overexpression of Ccne1 with Ndufa6 resulted in Myh4 expression decrease and the number of S-phase cells slight increase. Together, our results suggested that TEAD1 may mediate muscle development through its target genes, Mrpl21, Ndufa6 and Ccne1.