RRC ID 75871
Author Quillien A, Gilbert G, Boulet M, Ethuin S, Waltzer L, Vandel L.
Title Prmt5 promotes vascular morphogenesis independently of its methyltransferase activity.
Journal PLoS Genet
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 in blood vessel formation as well as hematopoiesis using zebrafish as a model system. Through the combination of different prmt5 loss-of-function approaches we highlighted a key role of Prmt5 in both processes. Notably, we showed that Prmt5 promotes vascular morphogenesis through the transcriptional control of ETS transcription factors and adhesion proteins in endothelial cells. Interestingly, using a catalytic dead mutant of Prmt5 and a specific drug inhibitor, we found that while Prmt5 methyltransferase activity was required for blood cell formation, it was dispensable for vessel formation. Analyses of chromatin architecture impact on reporter genes expression and chromatin immunoprecipitation experiments led us to propose that Prmt5 regulates transcription by acting as a scaffold protein that facilitates chromatin looping to promote vascular morphogenesis.
Volume 17(6)
Pages e1009641
Published 2021-6-1
DOI 10.1371/journal.pgen.1009641
PMID 34153034
PMC PMC8248709
MeSH Animals Base Sequence Chromatin / chemistry Chromatin / metabolism Embryo, Nonmammalian Endothelial Cells / cytology Endothelial Cells / metabolism Gene Expression Regulation, Developmental* Hematopoiesis / genetics* Morphogenesis / genetics* Mutation Neovascularization, Physiologic / genetics* Protein Isoforms / genetics Protein Isoforms / metabolism Protein-Arginine N-Methyltransferases / genetics* Protein-Arginine N-Methyltransferases / metabolism Proto-Oncogene Proteins c-ets / genetics* Proto-Oncogene Proteins c-ets / metabolism Signal Transduction Transcription, Genetic Zebrafish / genetics* Zebrafish / growth & development Zebrafish / metabolism Zebrafish Proteins / genetics* Zebrafish Proteins / metabolism
IF 5.175
Zebrafish UAS:GFP