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Stress-induced RNA–chromatin interactions promote endothelial dysfunction

Author

Listed:
  • Riccardo Calandrelli

    (University of California San Diego)

  • Lixia Xu

    (Guangdong Academy of Medical Sciences
    Beckman Research Institute, City of Hope)

  • Yingjun Luo

    (Beckman Research Institute, City of Hope)

  • Weixin Wu

    (University of California San Diego)

  • Xiaochen Fan

    (University of California San Diego)

  • Tri Nguyen

    (University of California San Diego)

  • Chien-Ju Chen

    (University of California San Diego)

  • Kiran Sriram

    (Beckman Research Institute, City of Hope
    Irell and Manella Graduate School of Biological Sciences, City of Hope)

  • Xiaofang Tang

    (Beckman Research Institute, City of Hope)

  • Andrew B. Burns

    (Beckman Research Institute, City of Hope)

  • Rama Natarajan

    (Beckman Research Institute, City of Hope
    Irell and Manella Graduate School of Biological Sciences, City of Hope)

  • Zhen Bouman Chen

    (Beckman Research Institute, City of Hope
    Irell and Manella Graduate School of Biological Sciences, City of Hope)

  • Sheng Zhong

    (University of California San Diego)

Abstract

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.

Suggested Citation

  • Riccardo Calandrelli & Lixia Xu & Yingjun Luo & Weixin Wu & Xiaochen Fan & Tri Nguyen & Chien-Ju Chen & Kiran Sriram & Xiaofang Tang & Andrew B. Burns & Rama Natarajan & Zhen Bouman Chen & Sheng Zhong, 2020. "Stress-induced RNA–chromatin interactions promote endothelial dysfunction," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18957-w
    DOI: 10.1038/s41467-020-18957-w
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    Cited by:

    1. Riccardo Calandrelli & Xingzhao Wen & John Lalith Charles Richard & Zhifei Luo & Tri C. Nguyen & Chien-Ju Chen & Zhijie Qi & Shuanghong Xue & Weizhong Chen & Zhangming Yan & Weixin Wu & Kathia Zaleta-, 2023. "Genome-wide analysis of the interplay between chromatin-associated RNA and 3D genome organization in human cells," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Young-Woong Kim & Greta Zara & HyunJun Kang & Sergio Branciamore & Denis O’Meally & Yuxin Feng & Chia-Yi Kuan & Yingjun Luo & Michael S. Nelson & Alex B. Brummer & Russell Rockne & Zhen Bouman Chen & , 2022. "Integration of single-cell transcriptomes and biological function reveals distinct behavioral patterns in bone marrow endothelium," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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