The transcription factors GATA4, GATA5 and GATA6 are important regulators of heart muscle differentiation (cardiomyogenesis), which function in a partially redundant manner. We identified genes specifically regulated by individual cardiogenic GATA factors in a genome-wide transcriptomics analysis. The genes regulated by gata4 are particularly interesting because GATA4 is able to induce differentiation of beating cardiomyocytes in Xenopus and in mammalian systems. Among the specifically gata4-regulated transcripts we identified two SoxF family members, sox7 and sox18. Experimental reinstatement of gata4 restores sox7 and sox18 expression, and loss of cardiomyocyte differentiation due to gata4 knockdown is partially restored by reinstating sox7 or sox18 expression, while (as previously reported) knockdown of sox7 or sox18 interferes with heart muscle formation. In order to test for conservation in mammalian cardiomyogenesis, we confirmed in mouse embryonic stem cells (ESCs) undergoing cardiomyogenesis that knockdown of Gata4 leads to reduced Sox7 (and Sox18) expression and that Gata4 is also uniquely capable of promptly inducing Sox7 expression. Taken together, we identify an important and conserved gene regulatory axis from gata4 to the SoxF paralogs sox7 and sox18 and further to heart muscle cell differentiation.
Bibliographical noteThis work was supported by British Heart Foundation (BHF Project Grant no
PG/13/23/30080 to B.A.A and S.H.), Biotechnology and Biological Sciences Research Council (BB/M001695/1 to S.H.) and the University of Aberdeen (for A.T.L).
We’re grateful to Ms Yvonne Turnbull and Ms Kate Watt for technical assistance and lab management. We would like to thank Professor Cedric Blanpain and Dr Xionghui Li from Université Libre de Bruxelles for providing training of ES cell manipulation and Mesp1/Gata4 cell lines. We are grateful to Professor Todd Evans from Weill Cornell Medical College for generously providing iGata ES cell lines. We also would like to thank Professor Aaron Zorn and Scott Rankin for providing Xsox18 plasmid.
- GATA factors
- sox factors
- heart muscle
- embryonic stem cells
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- School of Medicine, Medical Sciences & Nutrition, Cardiometabolic Disease
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Cardiovascular and Diabetes Centre
- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Personal Chair
- School of Medicine, Medical Sciences & Nutrition, Institute of Medical Sciences