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Nat Commun. 2018 Jan 16;9(1):237. doi: 10.1038/s41467-017-02431-1.

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

Author information

1
Institute for Cardiovascular Regeneration, Goethe University, Theodor-Stern-Kai 7, Frankfurt am Main, 60590, Germany.
2
German Center of Cardiovascular Research (DZHK), Frankfurt am Main, 60590, Germany.
3
Institute of Biochemistry, Justus-Liebig-University, Heinrich-Buff-Ring 17, Giessen, 35392, Germany.
4
Max Planck Institute for Heart and Lung Research, Ludwigstraße 43, Bad Nauheim, 61231, Germany.
5
Institute for Cardiovascular Regeneration, Goethe University, Theodor-Stern-Kai 7, Frankfurt am Main, 60590, Germany. dimmeler@em.uni-frankfurt.de.
6
German Center of Cardiovascular Research (DZHK), Frankfurt am Main, 60590, Germany. dimmeler@em.uni-frankfurt.de.

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.

PMID:
29339785
PMCID:
PMC5770451
DOI:
10.1038/s41467-017-02431-1
[Indexed for MEDLINE]
Free PMC Article

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