Background:
Long non-coding RNAs (lncRNAs) are described as molecular switches in cellular differentiation, movement and in the reprogramming of cell states by altering gene expression patterns. However, in endothelial cells their role is not well understood. We identified LINC00607 as a novel and functionally important endothelial-enriched lncRNA securing the endothelial phenotype.

Results:
LINC00607 is among the ten highest expressed lncRNAs in endothelial cells, as shown by deep-endothelial RNA-seq and FANTOM5 search. As a response to hypoxia, LINC00607 is among the highest induced lncRNAs. Silencing of LINC00607 with siRNAs or LentiCRISPR-knockout in human endothelial cells increased cellular proliferation and inhibited angiogenic sprouting in response to VEGF-A. Anti-sense oligo pulldown of the predominantly nuclear lncRNA followed by Mass spectrometry revealed the chromatin remodeler SMARCA3 and the DNA-binding protein SSBP1 as protein interaction partners. Chromatin remodeling is a dynamic epigenetic process leading to modifications in chromatin architecture. Thereby altering the access of the transcriptional machinery to the chromatin. CRISPR-mediated endothelial cell knockout of LINC00607 followed by RNA-Seq revealed important phenotypic cues for LINC00607: Genes related to endothelial function including FLT1, Cadherins, PECAM1 and VWF, were strongly downregulated, whereas genes involved in TGFß- and NOTCH-signaling pathways were upregulated upon loss of LINC00607. The results indicate that LINC00607 might function as a guide for SMARCA3 and SSBP1 them to specific target sites to maintain endothelial function.