NKX2-5 Regulates the Expression of beta-Catenin and GATA4 in Ventricular Myocytes

作者：Riazi Ali M^*; Takeuchi Jun K; Hornberger Lisa K; Zaidi Syed Hassan; Amini Fariba; Coles John; Bruneau Benoit G; Van Arsdell Glen S

来源：PLos One, 2009, 4(5): e5698.

DOI：10.1371/journal.pone.0005698

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.

• 出版日期2009-5-28