MEF2 transcription factors are key regulators of sprouting angiogenesis

摘要: Angiogenesis, the fundamental process by which new blood vessels form from existing ones, depends on precise spatial and temporal gene expression within specific compartments of endothelium. However, molecular links between proangiogenic signals downstream remain unclear. During sprouting angiogenesis, specification endothelial cells into tip that lead vessel sprouts is coordinated vascular growth factor A (VEGFA) Delta-like ligand 4 (Dll4)/Notch signaling requires high levels Notch DLL4. Here, we identify MEF2 transcription factors as crucial regulators angiogenesis directly VEGFA. Through characterization a Dll4 enhancer directing to at angiogenic front, found transcriptionally activate many other key genes up-regulated during in both physiological tumor vascularization. Unlike ETS-mediated regulation, MEF2-binding motifs are not ubiquitous all enhancers promoters but instead overrepresented around associated with angiogenesis. target activation linked VEGFA-induced release repressive histone deacetylases concurrent recruitment acetyltransferase EP300 regulatory elements, thus establishing transcriptional effectors VEGFA