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| Item Type: | Article |
|---|---|
| Title: | The endothelial transcription factor ERG mediates angiopoietin-1-dependent control of notch signalling and vascular stability |
| Creators Name: | Shah, A.V., Birdsey, G.M., Peghaire, C., Pitulescu, M.E., Dufton, N.P., Yang, Y., Weinberg, I., Osuna Almagro, L., Payne, L., Mason, J.C., Gerhardt, H., Adams, R.H. and Randi, A.M. |
| Abstract: | Notch and Angiopoietin-1 (Ang1)/Tie2 pathways are crucial for vascular maturation and stability. Here we identify the transcription factor ERG as a key regulator of endothelial Notch signalling. We show that ERG controls the balance between Notch ligands by driving Delta-like ligand 4 (Dll4) while repressing Jagged1 (Jag1) expression. In vivo, this regulation occurs selectively in the maturing plexus of the mouse developing retina, where Ang1/Tie2 signalling is active. We find that ERG mediates Ang1-dependent regulation of Notch ligands and is required for the stabilizing effects of Ang1 in vivo. We show that Ang1 induces ERG phosphorylation in a phosphoinositide 3-kinase (PI3K)/Akt-dependent manner, resulting in ERG enrichment at Dll4 promoter and multiple enhancers. Finally, we demonstrate that ERG directly interacts with Notch intracellular domain (NICD) and {beta}-catenin and is required for Ang1-dependent {beta}-catenin recruitment at the Dll4 locus. We propose that ERG coordinates Ang1, {beta}-catenin and Notch signalling to promote vascular stability. |
| Keywords: | Angiopoietin-1, Human Umbilical Vein Endothelial Cells, Inbred C57BL Mice, Intercellular Signaling Peptides and Proteins, Jagged-1 Protein, Notch Receptors, Phosphatidylinositol 3-Kinases, Phosphorylation, Proto-Oncogene Proteins c-akt, Transcriptional Regulator ERG, Vascular Remodeling, Wnt Signaling Pathway, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 8 |
| Page Range: | 16002 |
| Date: | 11 July 2017 |
| Official Publication: | https://doi.org/10.1038/ncomms16002 |
| PubMed: | View item in PubMed |
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