Mary Wilson
Well-known member
18 Aug 2023
Vol 9, Issue 33
DOI: 10.1126/sciadv.adg5211
MING KUANG 3, YINGCHI ZHAO, HAITAO YU, SIJI LI, TIANYI LIU, LUOYING CHEN, JINGXUAN CHEN, YUJIE LUO, XUEFEI GUO, XUEMEI WEI, YUNFEI LI, ZEMING ZHANG, DANDAN WANG, AND FUPING YOU
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.
https://www.science.org/doi/10.1126/sciadv.adg5211
Vol 9, Issue 33
DOI: 10.1126/sciadv.adg5211
MING KUANG 3, YINGCHI ZHAO, HAITAO YU, SIJI LI, TIANYI LIU, LUOYING CHEN, JINGXUAN CHEN, YUJIE LUO, XUEFEI GUO, XUEMEI WEI, YUNFEI LI, ZEMING ZHANG, DANDAN WANG, AND FUPING YOU
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.
https://www.science.org/doi/10.1126/sciadv.adg5211