Stress-induced RNA-chromatin interactions promote endothelial dysfunction.
Riccardo CalandrelliLixia XuYingjun LuoWeixin WuXiaochen FanTri NguyenChien-Ju ChenKiran SriramXiaofang TangAndrew B BurnsRama NatarajanZhen Bouman ChenSheng ZhongPublished in: Nature communications (2020)
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 TNFα (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.
Keyphrases
- gene expression
- high glucose
- genome wide
- dna damage
- rna seq
- single cell
- transcription factor
- stress induced
- nucleic acid
- endothelial cells
- dna methylation
- poor prognosis
- oxidative stress
- type diabetes
- rheumatoid arthritis
- copy number
- long non coding rna
- binding protein
- metabolic syndrome
- climate change
- high throughput
- signaling pathway
- heat stress
- wound healing
- genome wide identification