Dynamic changes in RNA-chromatin interactome promote endothelial dysfunction

Riccardo Calandrelli, Lixia Xu, Yingjun Luo, Weixin Wu, Xiaochen Fan, Tri Nguyen, Chienju Chen, Kiran Sriram, Rama Natarajan, Zhen Bouman-Chen, Sheng Zhong

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Received Date: 23rd July 19

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 TNFα, 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 TNFα-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. 

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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