Dynamic changes in RNA-chromatin interactome promote endothelial dysfunction
Calandrelli, R.; Xu, L.; Luo, Y.; Wu, W.; Fan, X.; Nguyen, T.; Chen, C.; Sriram, K.; Natarajan, R.; Chen, Z.; Zhong, S.
Show abstract
Chromatins are pervasively attached by RNAs. Here, we asked whether global RNA-chromatin contacts are altered in a given cell type in a disease context, and whether these alterations impact gene expression and cell function. In endothelial cells (ECs) treated by high-glucose and TNF, we employed single-cell RNA-sequencing and in situ mapping of RNA-genome interaction (iMARGI) assay to delineate temporal changes in transcriptome and RNA-chromatin interactome. ECs displayed dramatic and heterogeneous changes in single cell transcriptome, accompanied by a dynamic and strong increase in inter-chromosomal RNA-DNA interactions, particularly among super enhancers (SEs). These SEs overlap with genes contributing to inflammatory response and endothelial mesenchymal transition (EndoMT), two key aspects of endothelial dysfunction. Perturbation of a high-glucose and TNF-activated interaction involving SEs overlapping LINC00607 and SERPINE1 attenuated the pro-inflammatory and pro-EndoMT gene induction and EC dysfunction. Our findings highlight RNA-chromatin contacts as a crucial regulatory feature in biological and disease processes, exemplified by endothelial dysfunction, a major mediator of numerous diseases.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Chromatin interaction maps of human arterioles reveal new mechanisms for the genetic regulation of blood pressure 96%
- LETR1 is a lymphatic endothelial-specific lncRNA that governs cell proliferation and migration through KLF4 and SEMA3C 96%
- HIF1α-AS1 is a DNA:DNA:RNA triplex-forming lncRNA interacting with the HUSH complex 96%
Similar papers in this journal
- DNA motif analysis of shear stress responsive endothelial enhancers reveals differential association of KLF and ETV/ETS binding sites with gained and lost enhancers 96%
- Ox-LDL induces a non-inflammatory response enriched for coronary artery disease risk in human endothelial cells 96%
- ACE2 protein expression within isogenic cell lines is heterogeneous and associated with distinct transcriptomes 94%
Similar papers in this journal
- Single cell transcriptome analysis of cavernous tissues reveals the key roles of pericytes in diabetic erectile dysfunction 95%
- Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops 94%
- Robust single nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity 94%
Similar papers in this journal
- Mapping atherogenesis mechanisms in smooth muscle cells by targeting genes linked to coronary artery disease 95%
- Confined migration induces heterochromatin formation and alters chromatin accessibility 94%
- Dissecting the Cellular Landscape and Transcriptome Network in Viral Myocarditis by Single-Cell RNA Sequencing 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.