Suv4-20h2 protects against influenza virus infection by suppression of chromatin loop formation

Masami Shiimori, Yu Ichida, Ryota Nukiwa, Toshie Sakuma, Haruka Abe, Rei Kajitani, Yuji Fujino, Akira Kikuchi, Takeshi Kawamura, Tatsuhiko Kodama, Shinichi Toyooka, Katsuhiko Shirahige, Gunnar Schotta, Keiji Kuba, Takehiko Itoh, Yumiko Imai

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number102660
JournaliScience
Volume24
Issue number6
DOIs
Publication statusPublished - Jun 25 2021
Externally publishedYes

Keywords

  • Epigenetics
  • Molecular biology
  • Omics
  • Virology

ASJC Scopus subject areas

  • General

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