Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1
Copyright policy )Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1
JmjC domain-containing proteins play a crucial role in the control of gene expression by acting as protein hydroxylases or demethylases, thereby controlling histone methylation or splicing. Here, we demonstrate that silencing of Jumonji domain-containing protein 6 (Jmjd6) impairs angiogenic functions of endothelial cells by changing the gene expression and modulating the splicing of the VEGF-receptor 1 (Flt1). Reduction of Jmjd6 expression altered splicing of Flt1 and increased the levels of the soluble form of Flt1, which binds to VEGF and placental growth factor (PlGF) and thereby inhibits angiogenesis. Saturating VEGF or PlGF or neutralizing antibodies directed against soluble Flt1 rescued the angiogenic defects induced by Jmjd6 silencing. Jmjd6 interacts with the splicing factors U2AF65 that binds to Flt1 mRNA. In conclusion, Jmjd6 regulates the splicing of Flt1, thereby controlling angiogenic sprouting.
- Max Planck Institute for Heart and Lung Research Germany
- Max Planck Society Germany
- Justus Liebig University Giessen Germany
- University of Edinburgh United Kingdom
- Goethe University Frankfurt Germany
Vascular Endothelial Growth Factor A, Jumonji Domain-Containing Histone Demethylases, Vascular Endothelial Growth Factor Receptor-1, RNA Splicing, Neovascularization, Physiologic, Pregnancy Proteins, Gene Expression Regulation, Humans, Endothelium, Vascular, Gene Silencing, Protein Processing, Post-Translational, Cells, Cultured, Placenta Growth Factor
Vascular Endothelial Growth Factor A, Jumonji Domain-Containing Histone Demethylases, Vascular Endothelial Growth Factor Receptor-1, RNA Splicing, Neovascularization, Physiologic, Pregnancy Proteins, Gene Expression Regulation, Humans, Endothelium, Vascular, Gene Silencing, Protein Processing, Post-Translational, Cells, Cultured, Placenta Growth Factor
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).128 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!