Regulates Lineage Decisions in Cardiovascular Progenitor Cells.

Specification of the mesodermal lineages requires a complex set of morphogenetic events orchestrated by interconnected signaling pathways and gene regulatory networks. The transcription factor has critical functions in differentiation of multiple mesodermal lineages, including cardiac, endothelial, and hematopoietic. Using a doxycycline-inducible mouse embryonic stem cell line, we have previously shown that expression of in cardiovascular progenitor cells promotes expansion of endothelial progenitor cells (EPCs). In this study, we show that the ability of to promote endothelial cell fate occurs at the expense of the cardiac lineage. Using ChIP-Seq coupled with ATAC-Seq we identify downstream target genes of in cardiovascular progenitor cells and by integrating these data with transcriptomic analyses, we define -dependent gene programs specific to cardiac and EPCs. Furthermore, we demonstrate a protein-protein interaction between SOX7 and GATA4 and provide evidence that SOX7 interferes with the transcriptional activity of GATA4 on cardiac genes. In addition, we show that modulates WNT and BMP signaling during cardiovascular differentiation. Our data represent the first genome-wide analysis of function and reveal a critical role for in regulating signaling pathways that affect cardiovascular progenitor cell differentiation.