| First Author | Riazi AM | Year | 2009 |
| Journal | PLoS One | Volume | 4 |
| Issue | 5 | Pages | e5698 |
| PubMed ID | 19479054 | Mgi Jnum | J:149314 |
| Mgi Id | MGI:3848291 | Doi | 10.1371/journal.pone.0005698 |
| Citation | Riazi AM, et al. (2009) NKX2-5 regulates the expression of beta-catenin and GATA4 in ventricular myocytes. PLoS One 4(5):e5698 |
| abstractText | BACKGROUND: The molecular pathway that controls cardiogenesis is temporally and spatially regulated by master transcriptional regulators such as NKX2-5, Isl1, MEF2C, GATA4, and beta-catenin. The interplay between these factors and their downstream targets are not completely understood. Here, we studied regulation of beta-catenin and GATA4 by NKX2-5 in human fetal cardiac myocytes. METHODOLOGY/PRINCIPAL FINDINGS: Using antisense inhibition we disrupted the expression of NKX2-5 and studied changes in expression of cardiac-associated genes. Down-regulation of NKX2-5 resulted in increased beta-catenin while GATA4 was decreased. We demonstrated that this regulation was conferred by binding of NKX2-5 to specific elements (NKEs) in the promoter region of the beta-catenin and GATA4 genes. Using promoter-luciferase reporter assay combined with mutational analysis of the NKEs we demonstrated that the identified NKX2-5 binding sites were essential for the suppression of beta-catenin, and upregulation of GATA4 by NKX2-5. CONCLUSIONS: This study suggests that NKX2-5 modulates the beta-catenin and GATA4 transcriptional activities in developing human cardiac myocytes. |
