小柯机器人

美国斯坦福大学Howard Y. Chang研究组表明B细胞特异的XIST复合物可强制X染色体灭活并抑制非典型B细胞。2021年3月17日，《细胞》杂志发表了这一成果。

他们显示成年人B细胞中不断需要XIST来沉默X连锁免疫基因（例如TLR7）的亚群。XIST依赖的基因缺乏启动子DNA甲基化，并需要连续的XIST依赖的组蛋白去乙酰化。XIST RNA导向的蛋白质组学和CRISPRi筛选揭示了独特的体细胞类型特异性XIST复合物，并鉴定了能够介导Pol II暂停B细胞中X连锁基因启动子的TRIM28。

患有系统性红斑狼疮或COVID-19感染的女性患者的单细胞转录组数据显示，CD11c +非典型记忆B细胞（ABCs）的XIST失调反映了XIST依赖性基因的逃逸。用TLR7激动剂进行XIST灭活足以促进同种型转换的ABC。

这些结果表明长非编码RNA（lncRNA）-蛋白质复合物的细胞类型特异性多样化和功能，并暗示了XIST在生物学和医学上的性别差异中的扩展作用。

据悉，lncRNA XIST在早期发育中会在雌性细胞中建立X染色体失活（XCI），此后被认为在很大程度上是必需的。

附：英文原文

Title: B cell-specific XIST complex enforces X-inactivation and restrains atypical B cells

Author: Bingfei Yu, Yanyan Qi, Rui Li, Quanming Shi, Ansuman T. Satpathy, Howard Y. Chang

Issue&Volume: 2021-03-17

Abstract: The long non-coding RNA (lncRNA) XIST establishes X chromosome inactivation (XCI)in female cells in early development and thereafter is thought to be largely dispensable.Here, we show XIST is continually required in adult human B cells to silence a subsetof X-linked immune genes such as TLR7. XIST-dependent genes lack promoter DNA methylation and require continual XIST-dependenthistone deacetylation. XIST RNA-directed proteomics and CRISPRi screen reveal distinctivesomatic cell-type-specific XIST complexes and identify TRIM28 that mediates Pol IIpausing at promoters of X-linked genes in B cells. Single-cell transcriptome dataof female patients with either systemic lupus erythematosus or COVID-19 infectionrevealed XIST dysregulation, reflected by escape of XIST-dependent genes, in CD11c+ atypical memory B cells (ABCs). XIST inactivation with TLR7 agonism suffices to promoteisotype-switched ABCs. These results indicate cell-type-specific diversification andfunction for lncRNA-protein complexes and suggest expanded roles for XIST in sex-differencesin biology and medicine.

DOI: 10.1016/j.cell.2021.02.015

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00165-3