Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1

Jes Niels Boeckel, Virginia Guarani, Masamichi Koyanagi, Tino Roexe, Andreas Lengeling, Ralph T. Schermuly, Pascal Gellert, Thomas Braun, Andreas Zeiher, Stefanie Dimmeler

Research output: Contribution to journalArticlepeer-review

98 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3276-3281
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number8
DOIs
Publication statusPublished - Feb 22 2011

All Science Journal Classification (ASJC) codes

  • General

Fingerprint Dive into the research topics of 'Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1'. Together they form a unique fingerprint.

Cite this