Skip to main content
eScholarship
Open Access Publications from the University of California

UCSF

UC San Francisco Previously Published Works bannerUCSF

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

  • Author(s): Riazi, Ali M
  • Takeuchi, Jun K
  • Hornberger, Lisa K
  • Zaidi, Syed Hassan
  • Amini, Fariba
  • Coles, John
  • Bruneau, Benoit G
  • Van Arsdell, Glen S
  • et al.
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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View