TY  - JOUR
A1  - Neumann, Philipp
A1  - Jaé, Nicolas Christopher
A1  - Knau, Andrea
A1  - Glaser, Simone F.
A1  - Fouani, Youssef
A1  - Rossbach, Oliver
A1  - Krüger, Marcus
A1  - John, David
A1  - Bindereif, Albrecht
A1  - Grote, Phillip
A1  - Boon, Reinier
A1  - Dimmeler, Stefanie
T1  - The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2
T2  - Nature Communications
N2  - 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.
KW  - Angiogenesis
KW  - Histone post-translational modifications
KW  - Long non-coding RNAs
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45655
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-456555
SN  - 2041-1723
N1  - Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
VL  - 9
IS  - 1, Art. 237
SP  - 1
EP  - 12
PB  - Nature Publishing Group UK
CY  - [London]
ER  -