在NP220中介于非集成的逆转录病毒DNA的沉默
Yiping Zhu1,2,3, Gary Z Wang2,3, Oya Cingöz2,3
1Howard Hughes Medical Institute, Columbia University, New York, NY, USA.
Nature
|November 30, 2018
概括
外来DNA会触发天生的免疫力,导致未整合的逆转录病毒DNA的表观遗传沉默. 研究人员确定NP220和HUSH复合体是这种沉默机制的关键因素,对于控制病毒复制至关重要.
科学领域:
- 免疫学
- 表观遗传学
- 分子生物学
背景情况:
- 哺乳动物细胞具有与生俱来的免疫系统来对抗病原体感染.
- 外来DNA的进入,包括来自逆转录病毒,激活细胞反应.
- 不集成的逆转录病毒DNA被表观遗传沉默,限制了其转录.
研究的目的:
- 确定负责非集成逆转录病毒DNA表观遗传沉默的宿主因素.
- 阐明病毒DNA转录抑制的分子机制.
主要方法:
- 在人类细胞中进行全基因组CRISPR-Cas9查.
- 使用一种缺乏整合酶的MLV-GFP报告病毒.
- 染色体免疫沉试验
主要成果:
- 已确定NP220,HUSH复合物 (MPP8,TASOR,PPHLN1),SETDB1,HDAC1和HDAC4对于安静化至关重要.
- NP220作为HUSH复合体和表观遗传修饰物的关键招募剂.
- NP220淘汰会加速病毒复制.
结论:
- 这项研究揭示了抑制染色体外逆转录病毒DNA的分子机制.
- 在病毒DNA中招募沉默因子方面,NP220起着至关重要的作用.
- 了解这种途径对于控制逆转录病毒感染至关重要.
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