文章基本信息

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 等
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