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Dynamic changes in RNA-chromatin interactome promote endothelial dysfunction

View ORCID ProfileRiccardo Calandrelli, Lixia Xu, Yingjun Luo, Weixin Wu, Xiaochen Fan, Tri Nguyen, View ORCID ProfileChienju Chen, Kiran Sriram, Rama Natarajan, Zhen Bouman-Chen, View ORCID ProfileSheng Zhong
doi: https://doi.org/10.1101/712950
Riccardo Calandrelli
1Department of Bioengineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093
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  • ORCID record for Riccardo Calandrelli
Lixia Xu
2Guangdong People’s Hospital
3Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, 1500 Duarte Rd., Duarte, CA 91010
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Yingjun Luo
3Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, 1500 Duarte Rd., Duarte, CA 91010
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Weixin Wu
1Department of Bioengineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093
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Xiaochen Fan
1Department of Bioengineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093
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Tri Nguyen
1Department of Bioengineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093
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Chienju Chen
1Department of Bioengineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093
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Kiran Sriram
3Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, 1500 Duarte Rd., Duarte, CA 91010
4Irell and Manella Graduate School of Biological Sciences, City of Hope, 1500 Duarte Rd., Duarte, CA 91010
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Rama Natarajan
3Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, 1500 Duarte Rd., Duarte, CA 91010
4Irell and Manella Graduate School of Biological Sciences, City of Hope, 1500 Duarte Rd., Duarte, CA 91010
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Zhen Bouman-Chen
3Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, 1500 Duarte Rd., Duarte, CA 91010
4Irell and Manella Graduate School of Biological Sciences, City of Hope, 1500 Duarte Rd., Duarte, CA 91010
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  • For correspondence: zhenchen@coh.org szhong@eng.ucsd.edu
Sheng Zhong
1Department of Bioengineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093
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  • For correspondence: zhenchen@coh.org szhong@eng.ucsd.edu
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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 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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Posted July 24, 2019.
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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
bioRxiv 712950; doi: https://doi.org/10.1101/712950
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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
bioRxiv 712950; doi: https://doi.org/10.1101/712950

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