Journal article

Publication year: 2011

Pages: 3276-3281

Journal: Proceedings of the National Academy of Sciences

Volume number: 108

Issue number: 8

ISSN: 0027-8424

Open access status: Green

DOI Link: https://doi.org/10.1073/pnas.1008098108

Publisher: National Academy of Sciences

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.

Harvard Citation style: Boeckel, J., Guarani, V., Koyanagi, M., Roexe, T., Lengeling, A., Schermuly, R., et al. (2011) Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1, Proceedings of the National Academy of Sciences, 108(8), pp. 3276-3281. https://doi.org/10.1073/pnas.1008098108

APA Citation style: Boeckel, J., Guarani, V., Koyanagi, M., Roexe, T., Lengeling, A., Schermuly, R., Gellert, P., Braun, T., Zeiher, A., & Dimmeler, S. (2011). Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1. Proceedings of the National Academy of Sciences. 108(8), 3276-3281. https://doi.org/10.1073/pnas.1008098108