Meis 1 synergizes with nkx2.5 to repress isl1 transcription

Abstract The process of embryonic heart development is based on a spatially and temporally precise sequence of proliferation and differentiation of embryonic stem cells. This applies to every organ, but the large number of congenital cardiac malformations shows that the development of the heart is a particularly complex process. Understanding this in every detail is still subject of scientific research. It is already known that transcription factors and cofactors enable spatiotemporal control over the differentiation of cardiac progenitor cells into different cardiac cell lineages, such as cardiac muscle, endothelial, smooth muscle cells and fibroblasts through their different expression patterns and modes of function in networks. By performing DNA pulldown assay, immunoprecipitation and luciferase assay we addressed the role of the transcription factor Meis1 in cardiogenesis and, based on previous findings, investigated synergism with Nkx2.5 on the ISL1 enhancer, both known to be crucial factors in heart development. We found that Meis1 interacts with binding motifs in this enhancer. We also discovered a physical protein-protein interaction between Meis1 and Nkx2.5 and were able to confirm a synergistic inhibition of ISL1 promoter activity as hypothesized. These findings provide a basis for further experiments in human induced pluripotent stem cells, which may shed further light on the function of Meis1 in the network of factors involved in heart development.