RRC ID 67810
Author Shiimori M, Ichida Y, Nukiwa R, Sakuma T, Abe H, Kajitani R, Fujino Y, Kikuchi A, Kawamura T, Kodama T, Toyooka S, Shirahige K, Schotta G, Kuba K, Itoh T, Imai Y.
Title Suv4-20h2 protects against influenza virus infection by suppression of chromatin loop formation.
Journal iScience
Abstract The 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 infection in vivo. Thus, Suv4-20h2 acts as a safeguard against influenza virus infection by suppressing cohesin-mediated loop formation.
Volume 24(6)
Pages 102660
Published 2021-6-25
DOI 10.1016/j.isci.2021.102660
PII S2589-0042(21)00628-3
PMID 34169237
DNA material B6N Mouse BAC clone (RDB07573) B6Ng01-350C10 B6Ng01-237E10