特定于B细胞的XIST复合物强制X无活化并抑制非典型的B细胞
Bingfei Yu1, Yanyan Qi1, Rui Li1
1Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
Cell
|March 18, 2021
概括
在成年B细胞中,长非编码RNAXIST对于抑制TLR7等免疫基因至关重要. 它在狼和COVID-19等疾病中的失调凸显了性别差异的扩大作用.
科学领域:
- 遗传学
- 免疫学
- 表观遗传学
背景情况:
- 长非编码RNAXIST在早期发育过程中启动X染色体无活化 (XCI).
- 在最初的XCI建立后,XIST在很大程度上被认为是不可用的.
研究的目的:
- 研究XIST在成年人B细胞中的持续作用.
- 探索XIST在调节X链接免疫基因中的功能及其在疾病中的潜在参与.
主要方法:
- 通过XISTRNA导向的蛋白质组学和CRISPR干扰 (CRISPRi) 查.
- 来自系统性狼和COVID-19患者的单细胞转录组数据的分析.
- 研究了依赖XIST的基因调节,包括DNA甲基化和基因素脱乙化.
主要成果:
- 在成年人B细胞中,XIST不断地被要求使特定的X相关免疫基因,包括TLR7沉默.
- 依赖XIST的基因的特征是缺乏促进体DNA甲基化,并且需要持续的基因组脱化.
- TRIM28被确定为B细胞中XIST复合体的关键组成部分,在X链接基因促进体中调解Pol II暂停.
- 在患有狼或COVID-19的女性患者的CD11c+非典型记忆B细胞 (ABC) 中观察到XIST失调和XIST依赖基因的逃逸.
- 结合XIST无活化和TLR7激动,促进了同型切换ABC.
结论:
- 通过不同的lncRNA-蛋白质复合体,XIST表现出细胞类型特异性的功能.
- 在成年B细胞中,XIST在调节免疫基因表达方面发挥着至关重要的作用.
- XIST失调有助于疾病的发生,并突出其在基于性别的生物学差异和医学上的意义.
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