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标题：Suv4-20h2 protects against influenza virus infection by suppression of chromatin loop formation
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作者：Masami Shiimori ; Yu Ichida ; Ryota Nukiwa 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：6
页码：1-27
DOI：10.1016/j.isci.2021.102660
语种：English
出版社：Elsevier
摘要：SummaryThe spatial organization of chromatin is known to be highly dynamic in response to environmental stress. However, it remains unknown how chromatin dynamics contributes to or modulates disease pathogenesis. Here, we show that upon influenza virus infection, the H4K20me3 methyltransferase Suv4-20h2 binds the viral protein NP, which results in the inactivation of Suv4-20h2 and the dissociation of cohesin from Suv4-20h2. Inactivation of Suv4-20h2 by viral infection or genetic deletion allows the formation of an active chromatin loop at the HoxC8-HoxC6 loci coincident with cohesin loading. HoxC8 and HoxC6 proteins in turn enhance viral replication by inhibiting the Wnt-β-catenin mediated interferon response. Importantly, loss of Suv4-20h2 augments the pathology of influenza infectionin vivo. Thus, Suv4-20h2 acts as a safeguard against influenza virus infection by suppressing cohesin-mediated loop formation.Graphical abstractDisplay OmittedHighlights•H4K20me3 methyltransferase Suv4-20h2 suppresses influenza viral replication•Influenza virus NP protein binds to Suv4-20h2 and causes dissociation from cohesin•Suv4-20h2 inactivation generates cohesion-mediated loop formation at HoxC8 -HoxC6•HoxC8-HoxC6 enhance viral replication by suppressing Wnt/β-catenin signalingMolecular biology; Epigenetics; Virology; Omics