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

Author

Listed:
  • Philipp Neumann

    (Goethe University
    German Center of Cardiovascular Research (DZHK))

  • Nicolas Jaé

    (Goethe University
    German Center of Cardiovascular Research (DZHK))

  • Andrea Knau

    (Goethe University)

  • Simone F. Glaser

    (Goethe University
    German Center of Cardiovascular Research (DZHK))

  • Youssef Fouani

    (Goethe University)

  • Oliver Rossbach

    (Justus-Liebig-University)

  • Marcus Krüger

    (Max Planck Institute for Heart and Lung Research)

  • David John

    (Goethe University
    German Center of Cardiovascular Research (DZHK))

  • Albrecht Bindereif

    (Justus-Liebig-University)

  • Phillip Grote

    (Goethe University
    German Center of Cardiovascular Research (DZHK))

  • Reinier A. Boon

    (Goethe University
    German Center of Cardiovascular Research (DZHK))

  • Stefanie Dimmeler

    (Goethe University
    German Center of Cardiovascular Research (DZHK))

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.

Suggested Citation

  • 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 Dimmele, 2018. "The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02431-1
    DOI: 10.1038/s41467-017-02431-1
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