B cell-specific XIST complex enforces X-inactivation and restrains atypical B cells.
B cell-specific XIST complex enforces X-inactivation and restrains atypical B cells.
复制标题
B 细胞特异性 XIST 复合物强制 X 失活并抑制非典型 B 细胞。
DOI：
10.1016/j.cell.2021.02.015
复制
发表时间：
2021-04-01
期刊：
影响因子：
64.5
通讯作者：
Chang, Howard Y.
中科院分区：
文献类型：
--
作者：
Yu, Bingfei;Qi, Yanyan;Li, Rui;Shi, Quanming;Satpathy, Ansuman T.;Chang, Howard Y.
长链非编码RNA（lncRNA）XIST在早期发育的雌性细胞中建立X染色体失活（XCI），此后被认为在很大程度上失活。在这里，我们表明XIST是不断需要在成人B细胞沉默一个子集的X连锁免疫基因，如TLR 7。XIST依赖性基因缺乏启动子DNA甲基化，需要持续的XIST依赖性组蛋白脱乙酰化。XIST RNA指导的蛋白质组学和CRISPRi筛选揭示了独特的体细胞类型特异性XIST复合物，并鉴定了介导Pol II在B细胞中X连锁基因启动子处暂停的TRIM 28。系统性红斑狼疮或COVID-19感染女性患者的单细胞转录组数据显示，在CD 11 c+非典型记忆B细胞（ABC）中，XIST失调，反映为XIST依赖性基因的逃逸。XIST失活与TLR 7激动足以促进同种型转换的ABC。这些结果表明，细胞类型特异性的多样化和功能的lncRNA-蛋白质复合物，并建议扩大XIST在生物学和医学的性别差异的作用。XIST抑制人非典型B细胞发育。不同的XIST相关蛋白复合物有助于B细胞中XIST介导的基因沉默。
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 subset of X-linked immune genes such as TLR7. XIST-dependent genes lack promoter DNA methylation and require continual XIST-dependent histone deacetylation. XIST RNA-directed proteomics and CRISPRi screen reveal distinctive somatic cell-type-specific XIST complexes, and identify TRIM28 that mediates Pol II pausing at promoters of X-linked genes in B cells. Single-cell transcriptome data of female patients with either systemic lupus erythematosus or COVID-19 infection revealed XIST dysregulation, reflected by escape of XIST-dependent genes, in CD11c+ atypical memory B cells (ABCs). XIST inactivation with TLR7 agonism suffices to promote isotype-switched ABCs. These results indicate cell-type-specific diversification and function for lncRNA-protein complexes and suggest expanded roles for XIST in sex-differences in biology and medicine. XIST restrains human atypical B cell development. A distinct XIST-associated protein complex contributes to XIST-mediated gene silencing in B cells.
登录
查看更多内容
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
30.5
作者：
Arazi, Arnon;Rao, Deepak A.;Goldman, Daniel H.
通讯作者：
Goldman, Daniel H.
影响因子：
20.3
作者：
Hao, Yi;O'Neill, Patrick;Cancro, Michael P.
通讯作者：
Cancro, Michael P.
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK