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  • 标题:Genomic G-quadruplex folding triggers a cytokine-mediated inflammatory feedback loop to aggravate inflammatory diseases
  • 本地全文:下载
  • 作者:Xiaolin Wang ; Shunlun Chen ; Zhuoyang Zhao
  • 期刊名称:iScience
  • 印刷版ISSN:2589-0042
  • 出版年度:2022
  • 卷号:25
  • 期号:11
  • 页码:1-18
  • DOI:10.1016/j.isci.2022.105312
  • 语种:English
  • 出版社:Elsevier
  • 摘要:SummaryDNA G-quadruplex is a non-canonical secondary structure that could epigenetically regulate gene expression. To investigate the regulating role of G-quadruplex, we devised an integrating method to perform the algorithm profiling and genome-wide analysis for the dynamic change of genomic G-quadruplex and RNA profiles in rat nucleus pulposus cells by inducing G-quadruplex folding with multiple stabilizers. A group of genes potentially regulated by G-quadruplex and involved in the inflammation process has been identified. We found that G-quadruplex folding triggers inflammation response by upregulating inflammatory cytokines, which could promote G-quadruplex folding in a manner of positive feedback loop. Moreover, we confirmed that G-quadruplex is a marker indicating elevated inflammatory status and G-quadruplex folding facilitates the development of inflammatory diseases usingin vivointervertebral disc degeneration models. The crosstalk between G-quadruplex and inflammatory cytokines plays a vital role in regulating inflammation-derived diseases, which may provide new insights into the blocking target.Graphical abstractDisplay OmittedHighlights•G4-regulating genes are involved in the inflammation process•Inflammation and apoptosis triggered by G4 folding is a hallmark of disc degeneration•Inflammatory cytokines facilitate the genome-wide G4 folding•Crosstalk between G4 and inflammation provides new therapeutics for human diseasesBiological sciences; Immunology; Molecular biology; Molecular mechanism of gene regulation; Orthopedics
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