Send to

Choose Destination

See 1 citation found by title matching your search:

Nat Commun. 2017 Jul 11;8:16002. doi: 10.1038/ncomms16002.

The endothelial transcription factor ERG mediates Angiopoietin-1-dependent control of Notch signalling and vascular stability.

Author information

Vascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College London, London W12 0NN, UK.
Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Faculty of Medicine, University of Münster, D-48149 Münster, Germany.
Vascular Patterning Laboratory, Vesalius Research Center, VIB, KU Leuven, 3000 Leuven, Belgium &Max-Delbrück-Center for Molecular Medicine, Berlin 13125, Germany.


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center