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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. and Birdsey, G.M. and Peghaire, C. and Pitulescu, M.E. and Dufton, N.P. and Yang, Y. and Weinberg, I. and Osuna Almagro, L. and Payne, L. and Mason, J.C. and Gerhardt, H. and 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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