通过调节染色质可访问性,XAF1促进抗RNA病毒免疫反应
Ming Kuang1, Yingchi Zhao1, Haitao Yu1
1Institute 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.
Science advances
|August 18, 2023
概括
与X链接的亡蛋白抑制剂 (XAF1) 作为表观遗传调节剂,在RNA病毒感染期间打开染色质以促进抗病毒基因表达. 这种机制对于建立有效的抗病毒免疫反应至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 病毒学 病毒学
背景情况:
- 快速诱导抗病毒基因对于病毒清除至关重要.
- 这个过程需要转录因子和可访问的染色质,但感染期间染色质可访问性的调节尚不清楚.
研究的目的:
- 为了研究XAF1 (X-链接抑制剂的亡蛋白) 在调节病毒感染期间的染色质可访问性的作用.
- 阐明XAF1控制抗病毒基因表达的分子机制.
主要方法:
- 研究了XAF1与MAVS,TBK1,TRIM28和IRF1在RNA病毒感染时的相互作用.
- 评估了XAF1的TBK1-介导酸化对其核转位和与TRIM28.28的相互作用的影响.
- 研究了XAF1对TRIM28的脱SUMOylating活性及其对染色质可访问性和基因表达的影响.
- 使用XAF1缺乏的小鼠来评估XAF1在抗病毒免疫中的体内意义.
主要成果:
- XAF1作为表观遗传调节剂,在感染后释放被抑制的染色质.
- 在RNA病毒感染后,MAVS会招募XAF1和TBK1;TBK1酸化XAF1,促进核转位.
- 由IRF1指导的XAF1通过其PHD域准抗病毒基因位点,并通过TRIM28去SUMOylates,从而增加染色质的可访问性.
- 缺少XAF1的小鼠因抗病毒基因诱导受损而对RNA病毒表现出敏感性.
结论:
- XAF1是一个关键的表观遗传调节器,通过促进染色质开放来增强抗病毒免疫力.
- 在感染期间,XAF1-TRIM28相互作用是强大的抗病毒基因激活的关键.
- XAF1在对抗RNA病毒的宿主防御中起着至关重要的作用.
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