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Boos, Frederike; Oo, James A.; Warwick, Timothy; Günther, Stefan; Izquierdo Ponce, Judit; Lopez, Melina; Rafii, Diba; Buchmann, Giulia; Pham, Minh Duc; Msheik, Zahraa S.; Li, Tianfu; Seredinski, Sandra; Haydar, Shaza; Kashefiolasl, Sepide; Plate, Karl H.; Behr, Rüdiger; Mietsch, Matthias; Krishnan, Jaya; Pullamsetti, Soni S.; Bibli, Sofia-Iris; Hinkel, Rabea; Baker, Andrew H.; Boon, Reinier A.; Schulz, Marcel H.; [...]

The endothelial-enriched lncRNA LINC00607 mediates angiogenic function

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  • Medientyp: E-Artikel
  • Titel: The endothelial-enriched lncRNA LINC00607 mediates angiogenic function
  • Beteiligte: Boos, Frederike; Oo, James A.; Warwick, Timothy; Günther, Stefan; Izquierdo Ponce, Judit; Lopez, Melina; Rafii, Diba; Buchmann, Giulia; Pham, Minh Duc; Msheik, Zahraa S.; Li, Tianfu; Seredinski, Sandra; Haydar, Shaza; Kashefiolasl, Sepide; Plate, Karl H.; Behr, Rüdiger; Mietsch, Matthias; Krishnan, Jaya; Pullamsetti, Soni S.; Bibli, Sofia-Iris; Hinkel, Rabea; Baker, Andrew H.; Boon, Reinier A.; Schulz, Marcel H.; [...]
  • Erschienen: Springer Science and Business Media LLC, 2023
  • Erschienen in: Basic Research in Cardiology
  • Sprache: Englisch
  • DOI: 10.1007/s00395-023-00978-3
  • ISSN: 1435-1803
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Long non-coding RNAs (lncRNAs) can act as regulatory RNAs which, by altering the expression of target genes, impact on the cellular phenotype and cardiovascular disease development. Endothelial lncRNAs and their vascular functions are largely undefined. Deep RNA-Seq and FANTOM5 CAGE analysis revealed the lncRNA <jats:italic>LINC00607</jats:italic> to be highly enriched in human endothelial cells. <jats:italic>LINC00607</jats:italic> was induced in response to hypoxia, arteriosclerosis regression in non-human primates, post-atherosclerotic cultured endothelial cells from patients and also in response to propranolol used to induce regression of human arteriovenous malformations. siRNA knockdown or CRISPR/Cas9 knockout of <jats:italic>LINC00607</jats:italic> attenuated VEGF-A-induced angiogenic sprouting. <jats:italic>LINC00607</jats:italic> knockout in endothelial cells also integrated less into newly formed vascular networks in an in vivo assay in SCID mice. Overexpression of <jats:italic>LINC00607</jats:italic> in CRISPR knockout cells restored normal endothelial function. RNA- and ATAC-Seq after <jats:italic>LINC00607</jats:italic> knockout revealed changes in the transcription of endothelial gene sets linked to the endothelial phenotype and in chromatin accessibility around ERG-binding sites. Mechanistically, <jats:italic>LINC00607</jats:italic> interacted with the SWI/SNF chromatin remodeling protein BRG1. CRISPR/Cas9-mediated knockout of <jats:italic>BRG1</jats:italic> in HUVEC followed by CUT&amp;RUN revealed that BRG1 is required to secure a stable chromatin state, mainly on ERG-binding sites. In conclusion, <jats:italic>LINC00607</jats:italic> is an endothelial-enriched lncRNA that maintains ERG target gene transcription by interacting with the chromatin remodeler BRG1 to ultimately mediate angiogenesis.</jats:p>