GSE135354
Stress-induced RNA–chromatin interactions promote endothelial dysfunction (Hi-C)
Chromatin-associated RNA (caRNA) has been proposed as a type of epigenomic modifier. Here, we test whether environmental stress can induce cellular dysfunction through modulating RNA-chromatin interactions. We induce endothelial cell (EC) dysfunction with high glucose and TNFa (H?+?T), that mimic the common stress in diabetes mellitus. We characterize the H?+?T-induced changes in gene expression by single cell (sc)RNA-seq, DNA interactions by Hi-C, and RNA-chromatin interactions by iMARGI. H?+?T induce inter-chromosomal RNA-chromatin interactions, particularly among the super enhancers. To test the causal relationship between H?+?T-induced RNA-chromatin interactions and the expression of EC dysfunction-related genes, we suppress the LINC00607 RNA. This suppression attenuates the expression of SERPINE1, a critical pro-inflammatory and pro-fibrotic gene. Furthermore, the changes of the co-expression gene network between diabetic and healthy donor-derived ECs corroborate the H?+?T-induced RNA-chromatin interactions. Taken together, caRNA-mediated dysregulation of gene expression modulates EC dysfunction, a crucial mechanism underlying numerous diseases. Overall design: Map chromatin interactions in HUVEC human cell lines using Hi-C technique in three samples: control (no treatment) and after 3 and 7 days of treatment to mimic endothelial to mesenchymal transition.