The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2
- 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.
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| Author: | Philipp Neumann, Nicolas Christopher Jaé, Andrea Knau, Simone F. GlaserORCiDGND, Youssef FouaniGND, Oliver Rossbach, Marcus KrügerORCiDGND, David JohnORCiDGND, Albrecht BindereifORCiDGND, Phillip GroteORCiD, Reinier BoonORCiDGND, Stefanie DimmelerORCiDGND |
|---|---|
| URN: | urn:nbn:de:hebis:30:3-456555 |
| DOI: | https://doi.org/10.1038/s41467-017-02431-1 |
| ISSN: | 2041-1723 |
| Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/29339785 |
| Parent Title (English): | Nature Communications |
| Publisher: | Nature Publishing Group UK |
| Place of publication: | [London] |
| Document Type: | Article |
| Language: | English |
| Year of Completion: | 2018 |
| Date of first Publication: | 2018/01/16 |
| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
| Release Date: | 2018/02/13 |
| Tag: | Angiogenesis; Histone post-translational modifications; Long non-coding RNAs |
| Volume: | 9 |
| Issue: | 1, Art. 237 |
| Page Number: | 12 |
| First Page: | 1 |
| Last Page: | 12 |
| Note: | 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/. |
| HeBIS-PPN: | 426624327 |
| Institutes: | Medizin / Medizin |
| Exzellenzcluster / Exzellenzcluster Makromolekulare Komplexe | |
| Wissenschaftliche Zentren und koordinierte Programme / DFG-Forschergruppen | |
| Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
| Sammlungen: | Universitätspublikationen |
| Licence (German): |  Creative Commons - Namensnennung 4.0 |
