TEAD1 controls C2C12 cell proliferation and differentiation and regulates three novel target genes.

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. Crown