GATA4: orchestrating cardiac development and beyond

Cardiovascular Research, vol. 121, pp. 2476–2483

Abstract

Mammalian cardiac development and homeostasis rely on tightly coordinated transcriptional programs driven by core cardiogenic transcription factors. Among these, GATA binding protein 4 (GATA4) plays a pivotal role-not only in orchestrating embryonic heart formation, but also in modulating cardiac adaptation to physiological and pathological stress. To fulfil its canonical functions, emerging evidence reveals that GATA4 activity is shaped by a multilayered regulatory network involving chromatin dynamics, transcriptional and post-transcriptional inputs, and diverse post-translational modifications. In this review, we provide an integrated overview of the roles of GATA4 across developmental stages, postnatal physiology, and disease contexts. We further examine how chromatin occupancy and regulatory mechanisms fine-tune GATA4 function and evaluate current strategies that leverage GATA4 modulation for cardiac repair and regeneration. By highlighting both established and underexplored facets of GATA4 biology, this review establishes GATA4 as a central regulator of cardiac identity and plasticity, with broad implications for developmental biology, cardiac physiology, and therapeutic innovation.

Authors 5

1. Laura Heuvelmans

   Maastricht University

   Affiliation as printed

   Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Faculty of Health, Medicine and Life Sciences, Maastricht University , Universiteitssingel 50, 6229 ER Maastricht ,

2. Dylan Mostert Aachen DWI - Leibniz Institute for Interactive Materials

   Maastricht University · DWI – Leibniz Institute for Interactive Materials

   Affiliation as printed

   DWI—Leibniz-Institute for Interactive Materials , Forckenbeckstr. 50, Aachen 52074 ,

   Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Faculty of Health, Medicine and Life Sciences, Maastricht University , Universiteitssingel 50, 6229 ER Maastricht ,

3. Giulia Spanò

   Maastricht University

   Affiliation as printed

   Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Faculty of Health, Medicine and Life Sciences, Maastricht University , Universiteitssingel 50, 6229 ER Maastricht ,

4. Monika Stoll

   University of Münster · Maastricht University

   Affiliation as printed

   Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Faculty of Health, Medicine and Life Sciences, Maastricht University , Universiteitssingel 50, 6229 ER Maastricht ,

   Department of Genetic Epidemiology, Institute of Human Genetics, University of Münster , Domagkstraße 3, 48149 Münster ,

5. León J. De Windt corresponding

   Maastricht University

   Affiliation as printed

   Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Faculty of Health, Medicine and Life Sciences, Maastricht University , Universiteitssingel 50, 6229 ER Maastricht ,