Prmt5 promotes vascular morphogenesis independently of its methyltransferase activity.

Abstract

During development, the vertebrate vasculature undergoes major growth and remodeling. While the transcriptional cascade underlying blood vessel formation starts to be better characterized, little is known concerning the role and mode of action of epigenetic enzymes during this process. Here, we explored the role of the Protein Arginine Methyl Transferase Prmt5 during blood vessel formation and hematopoiesis in zebrafish. Through the generation of a prmt5 mutant, we highlighted a key role of Prmt5 in both hematopoiesis and blood vessel formation. Notably, we showed that Prmt5 promotes vascular morphogenesis through the transcriptional control of ETS transcription factors and adhesion proteins in endothelial cells. Interestingly, we found that Prmt5 methyltransferase activity is not required to regulate gene expression, and the comparison of chromatin architecture impact on reporter genes expression leads us to propose that Prmt5 rather regulates transcription by acting as a scaffold protein that facilitates chromatin looping in these cells.