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

Philipp Neumann, Nicolas Jaé, Andrea Knau, Simone F. Glaser, Youssef Fouani, Oliver Rossbach, Marcus Krüger, David John, Albrecht Bindereif, Phillip Grote, Reinier A. Boon, Stefanie Dimmeler

Research output: Contribution to journalArticlepeer-review

141 Scopus citations

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-β2-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.

Original languageEnglish
Article number237
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2018
Externally publishedYes

Fingerprint

Dive into the research topics of 'The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2'. Together they form a unique fingerprint.

Cite this