Shah, AV;
Birdsey, GM;
Peghaire, C;
Pitulescu, ME;
Dufton, NP;
Yang, Y;
Weinberg, I;
... Randi, AM; + view all
(2017)
The endothelial transcription factor ERG mediates Angiopoietin-1-dependent control of Notch signalling and vascular stability.
Nature Communications
, 8
, Article 16002. 10.1038/ncomms16002.
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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 β-catenin and is required for Ang1-dependent β-catenin recruitment at the Dll4 locus. We propose that ERG coordinates Ang1, β-catenin and Notch signalling to promote vascular stability.
| Type: | Article |
|---|---|
| Title: | The endothelial transcription factor ERG mediates Angiopoietin-1-dependent control of Notch signalling and vascular stability |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ncomms16002 |
| Publisher version: | http://dx.doi.org/10.1038/ncomms16002 |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, REGULATES ANGIOGENESIS, EMBRYONIC LETHALITY, DLL4 REGULATION, BLOOD-VESSELS, ARTERIAL, LIGAND, MICE, EXPRESSION, HOMEOSTASIS, PATHWAY |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10057364 |
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