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PLoS One. 2009 May 28;4(5):e5698. doi: 10.1371/journal.pone.0005698.

NKX2-5 regulates the expression of beta-catenin and GATA4 in ventricular myocytes.

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  • 1Labatt Family Heart Centre, Hospital for Sick Children, Toronto, Ontario, Canada. ali.riazi@sickkids.ca

Abstract

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.

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