XAF1 Promotes Anti-RNA Virus Immune Responses by Regulating Chromatin Accessibility

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2023 Aug 18

PMID 37595039

Authors

Ming Kuang

Yingchi Zhao

Haitao Yu

Siji Li

Tianyi Liu

Luoying Chen

Jingxuan Chen

Yujie Luo

Xuefei Guo

Xuemei Wei

Yunfei Li

Zeming Zhang

Dandan Wang

Fuping You

Affiliations

Soon will be listed here.

Abstract

A rapid induction of antiviral genes is critical for eliminating viruses, which requires activated transcription factors and opened chromatins to initiate transcription. However, it remains elusive how the accessibility of specific chromatin is regulated during infection. Here, we found that XAF1 functioned as an epigenetic regulator that liberated repressed chromatin after infection. Upon RNA virus infection, MAVS recruited XAF1 and TBK1. TBK1 phosphorylated XAF1 at serine-252 and promoted its nuclear translocation. XAF1 then interacted with TRIM28 with the guidance of IRF1 to the specific locus of antiviral genes. XAF1 de-SUMOylated TRIM28 through its PHD domain, which led to increased accessibility of the chromatin and robust induction of antiviral genes. XAF1-deficient mice were susceptible to RNA virus due to impaired induction of antiviral genes. Together, XAF1 acts as an epigenetic regulator that promotes the opening of chromatin and activation of antiviral immunity by targeting TRIM28 during infection.

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