Article (Scientific journals)
Dynamic regulation of VEGF-inducible genes by an ERK/ERG/p300 transcriptional network.
Fish, Jason E.; Cantu Gutierrez, Manuel; Dang, Lan T. et al.
2017In Development, 144 (13), p. 2428-2444
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Keywords :
Animals; Cattle; E1A-Associated p300 Protein/metabolism; Enhancer Elements, Genetic/genetics; Extracellular Signal-Regulated MAP Kinases/metabolism; Female; Gene Expression Regulation/drug effects; Gene Expression Regulation, Developmental/drug effects; Gene Regulatory Networks/drug effects; Human Umbilical Vein Endothelial Cells/drug effects/metabolism; Humans; Intercellular Signaling Peptides and Proteins/metabolism; Introns/genetics; MAP Kinase Signaling System/drug effects; Male; Mice; Neovascularization, Physiologic/genetics; Transcription, Genetic/drug effects; Transcriptional Regulator ERG/metabolism; Vascular Endothelial Growth Factor A/pharmacology; Zebrafish/embryology; Angiogenesis; ETS factor; Endothelial cell; Enhancer; Genome editing; Human; Mouse; Transcription; Zebrafish
Abstract :
[en] The transcriptional pathways activated downstream of vascular endothelial growth factor (VEGF) signaling during angiogenesis remain incompletely characterized. By assessing the signals responsible for induction of the Notch ligand delta-like 4 (DLL4) in endothelial cells, we find that activation of the MAPK/ERK pathway mirrors the rapid and dynamic induction of DLL4 transcription and that this pathway is required for DLL4 expression. Furthermore, VEGF/ERK signaling induces phosphorylation and activation of the ETS transcription factor ERG, a prerequisite for DLL4 induction. Transcription of DLL4 coincides with dynamic ERG-dependent recruitment of the transcriptional co-activator p300. Genome-wide gene expression profiling identified a network of VEGF-responsive and ERG-dependent genes, and ERG chromatin immunoprecipitation (ChIP)-seq revealed the presence of conserved ERG-bound putative enhancer elements near these target genes. Functional experiments performed in vitro and in vivo confirm that this network of genes requires ERK, ERG and p300 activity. Finally, genome-editing and transgenic approaches demonstrate that a highly conserved ERG-bound enhancer located upstream of HLX (which encodes a transcription factor implicated in sprouting angiogenesis) is required for its VEGF-mediated induction. Collectively, these findings elucidate a novel transcriptional pathway contributing to VEGF-dependent angiogenesis.
Disciplines :
Genetics & genetic processes
Author, co-author :
Fish, Jason E.;  Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.
Cantu Gutierrez, Manuel;  Cardiovascular Research Institute, Baylor College of Medicine, Houston
Dang, Lan T.;  Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.
Khyzha, Nadiya;  Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.
Chen, Zhiqi;  Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.
Veitch, Shawn;  Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.
Cheng, Henry S.;  Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.
Khor, Melvin;  Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.
Antounians, Lina;  Genetics and Genome Biology, Hospital for Sick Children, Toronto M5G 0A4, Canada.
Njock, Makon-Sébastien  ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Boudreau, Emilie;  Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.
Herman, Alexander M.;  Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Rhyner, Alexander M.;  Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Ruiz, Oscar E.;  Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Eisenhoffer, George T.;  Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Medina-Rivera, Alejandra;  Genetics and Genome Biology, Hospital for Sick Children, Toronto M5G 0A4, Canada.
Wilson, Michael D.;  Genetics and Genome Biology, Hospital for Sick Children, Toronto M5G 0A4, Canada.
Wythe, Joshua D.;  Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA
More authors (8 more) Less
Language :
English
Title :
Dynamic regulation of VEGF-inducible genes by an ERK/ERG/p300 transcriptional network.
Publication date :
01 July 2017
Journal title :
Development
ISSN :
0950-1991
eISSN :
1477-9129
Publisher :
The Company of Biologists, Cambridge, United Kingdom
Volume :
144
Issue :
13
Pages :
2428-2444
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) 2017. Published by The Company of Biologists Ltd.
Available on ORBi :
since 05 January 2018

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