XAF1 通过调节染色质可及性促进抗病毒免疫反应。
XAF1 promotes anti-RNA virus immune responses by regulating chromatin accessibility.
机构信息
Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, NHC Key Laboratory of Medical Immunology, Peking University Health Science Center, Beijing, China.
Ningbo first hospital, Ningbo hospital Zhejiang university, Ningbo, China.
出版信息
Sci Adv. 2023 Aug 18;9(33):eadg5211. doi: 10.1126/sciadv.adg5211.
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.
抗病毒基因的快速诱导对于清除病毒至关重要，这需要激活转录因子和打开染色质以启动转录。然而，在感染过程中，特定染色质的可及性如何被调节仍然难以捉摸。在这里，我们发现 XAF1 作为一种表观遗传调节剂，在感染后释放被抑制的染色质。在 RNA 病毒感染后，MAVS 招募 XAF1 和 TBK1。TBK1 在丝氨酸-252 位点磷酸化 XAF1，并促进其核转位。然后，XAF1 在 IRF1 的指导下与 TRIM28 相互作用，到达抗病毒基因的特定位置。XAF1 通过其 PHD 结构域使 TRIM28 去 SUMO 化，从而增加染色质的可及性，并强烈诱导抗病毒基因。由于抗病毒基因的诱导受损，XAF1 缺陷型小鼠易感染 RNA 病毒。总之，XAF1 作为一种表观遗传调节剂，通过在感染过程中靶向 TRIM28，促进染色质的开放和抗病毒免疫的激活。
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