Journalartikel

The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2


AutorenlisteNeumann, P; Jae, N; Knau, A; Glaser, SF; Fouani, Y; Rossbach, O; Krüger, M; John, D; Bindereif, A; Grote, P; Boon, RA; Dimmeler, S

Jahr der Veröffentlichung2018

Seiten237-

ZeitschriftNature Communications

Bandnummer9

Heftnummer1

ISSN2041-1723

eISSN2041-1723

Open Access StatusGold

DOI Linkhttps://doi.org/10.1038/s41467-017-02431-1

VerlagNature Research


Abstract
Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement of regulatory long non-coding RNAs in these processes is not well defined. Here, we show that the long non-coding antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator LOXL2 to regulate endothelial gene expression via changes in histone methylation. Using RNA deep sequencing, we find that GATA6-AS is upregulated in endothelial cells during hypoxia. Silencing of GATA6-AS diminishes TGF-beta 2-induced endothelial-mesenchymal transition in vitro and promotes formation of blood vessels in mice. We identify LOXL2, known to remove activating H3K4me3 chromatin marks, as a GATA6-AS-associated protein, and reveal a set of angiogenesis-related genes that are inversely regulated by LOXL2 and GATA6-AS silencing. As GATA6-AS silencing reduces H3K4me3 methylation of two of these genes, periostin and cyclooxygenase-2, we conclude that GATA6-AS acts as negative regulator of nuclear LOXL2 function.



Zitierstile

Harvard-ZitierstilNeumann, P., Jae, N., Knau, A., Glaser, S., Fouani, Y., Rossbach, O., et al. (2018) The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2, Nature Communications, 9(1), p. 237. https://doi.org/10.1038/s41467-017-02431-1

APA-ZitierstilNeumann, P., Jae, N., Knau, A., Glaser, S., Fouani, Y., Rossbach, O., Krüger, M., John, D., Bindereif, A., Grote, P., Boon, R., & Dimmeler, S. (2018). The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2. Nature Communications. 9(1), 237. https://doi.org/10.1038/s41467-017-02431-1



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