Dynamic regulation of VEGF-inducible genes by an ERK/ERG/p300 transcriptional network.

Autor:	Fish JE; Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada wythe@bcm.edu jason.fish@utoronto.ca.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada.; Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, Toronto M5S 3H2, Canada., Cantu Gutierrez M; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.; Graduate Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA., Dang LT; Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada.; Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, Toronto M5S 3H2, Canada., Khyzha N; Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada.; Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, Toronto M5S 3H2, Canada., Chen Z; Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada.; Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, Toronto M5S 3H2, Canada., Veitch S; Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada.; Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, Toronto M5S 3H2, Canada., Cheng HS; Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada.; Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, Toronto M5S 3H2, Canada., Khor M; Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada.; Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, Toronto M5S 3H2, Canada., Antounians L; Genetics and Genome Biology, Hospital for Sick Children, Toronto M5G 0A4, Canada.; Department of Molecular Genetics, University of Toronto, Toronto M5S 1A8, Canada., Njock MS; Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada.; Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, Toronto M5S 3H2, Canada., Boudreau E; Toronto General Hospital Research Institute, University Health Network, Toronto M5G 2C4, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada.; Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, Toronto M5S 3H2, Canada., Herman AM; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA., Rhyner AM; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA., Ruiz OE; Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Eisenhoffer GT; Graduate Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Graduate School of Biomedical Sciences, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA., Medina-Rivera A; Genetics and Genome Biology, Hospital for Sick Children, Toronto M5G 0A4, Canada.; Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Querétaro 76230, México., Wilson MD; Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, Toronto M5S 3H2, Canada.; Genetics and Genome Biology, Hospital for Sick Children, Toronto M5G 0A4, Canada.; Department of Molecular Genetics, University of Toronto, Toronto M5S 1A8, Canada., Wythe JD; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA wythe@bcm.edu jason.fish@utoronto.ca.; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.; Graduate Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2017 Jul 01; Vol. 144 (13), pp. 2428-2444. Date of Electronic Publication: 2017 May 23.
DOI:	10.1242/dev.146050
Abstrakt:	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. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2017. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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