Genome-wide transcriptomics analysis identifies sox7 and sox18 as specifically regulated by gata4 in cardiomyogenesis

Abstract

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.

Genome-wide transcriptomics analysis of genes regulated by GATA4, 5 and 6 during cardiomyogenesis in Xenopus laevis

“… The transcription factors GATA4, GATA5 and GATA6 play important roles in heart muscle differentiation. The data presented in this article are related to the research article entitled “Genome-wide transcriptomics analysis identifies sox7 and sox18 as specifically regulated by gata4 in cardiomyogenesis” (Afouda et al, 2017) [1] . The present study identifies genes regulated by these individual cardiogenic GATA factors using genome-wide transcriptomics analysis.…”

Three rare variants of SOX7 impairing its interaction with GATA4 may be a predisposing factor to complete AVSD

“…In the embryonic stem cell differentiation model, SOX7 affects the parietal endoderm by regulating GATA4 and GATA6 [36] . However, in the xenopus model, genome-wide transcriptomics analysis demonstrates that SOX7 is regulated by GATA4 directing cardiomyogenesis [30]. Doyle et al demonstrate a protein-protein interaction between SOX7 and GATA4 in cardiovascular progenitor cell differentiation [52].…”

“…Mouse models showed the complete or pan-endothelial knockout of SOX7 was embryonic lethal at E10.5 resulting from the cardiovascular defects [35]. In vitro embryonic stem cell differentiation has demonstrated that SOX7 affected the parietal endoderm differentiation through regulating GATA4 and GATA6 expression [36], while genome-wide transcriptomics analysis identi ed SOX7 as speci cally regulated by GATA4 in cardiomyogenesis in the xenopus model [30]. These data suggest that SOX7 plays vital roles in the morphogenesis of cardiovascular system.…”

“…SOX7 protein is highly expressed in cardiovascular tissues [27]. Many evidences have revealed that critical roles for SOX7 in cardiovascular development, especially in endothelial progenitor cells speci cation [28,29], myocardial differentiation [30], arteriovenous morphogenesis [31,32] and endothelium-hematopoietic transformation [33,34].…”

Transcriptome and DNA Methylome Dynamics during Triclosan-Induced Cardiomyocyte Differentiation Toxicity

“…Moreover, transcription factor GATA4, which is an important regulator of cardiomyogenesis, was also decreased after TCS exposure. The target genes of GATA4 were able to regulate CM beating [ 31 ]. Knocking down Gata4 in mESC during cardiomyogenesis led to decreased expression of Sox7 and heart muscle cell differentiation [ 31 ].…”