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

• DOI: 10.1038/s41467-017-02431-1
• Publication Date: 2018-01-10T12:22:55Z
• Authors: 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 Dimmeler
• Keywords: GATA6; H3K4me3

Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement regulatory long non-coding RNAs in these processes is not well defined. Here, we show that antisense transcript GATA6 (GATA6-AS) interacts with epigenetic regulator LOXL2 regulate gene expression via changes histone methylation. Using RNA deep sequencing, find GATA6-AS upregulated during hypoxia. Silencing diminishes TGF-β2-induced endothelial-mesenchymal transition vitro and promotes formation blood vessels mice. We identify LOXL2, known remove activating H3K4me3 chromatin marks, as a GATA6-AS-associated protein, reveal set angiogenesis-related genes are inversely regulated by silencing. As silencing reduces methylation two genes, periostin cyclooxygenase-2, conclude acts negative nuclear function.