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• W3119472332 abstract "SUMMARY The long noncoding 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-specific XIST complexes, and identify TRIM28 that mediates Pol II pausing at promoters of X-linked genes in B cells. XIST dysregylation, reflected by escape of XIST-dependent genes, occurs in CD11c+ atypical memory B cells across single-cell transcriptome data in patients with female-biased autoimmunity and COVID-19 infection. XIST inactivation with TLR7 agonism suffices to promote isotype-switched atypical B cells. These results suggest cell-type-specific diversification of lncRNA-protein complexes increase lncRNA functionalities, and expand roles for XIST in sex-differences in biology and medicine. HIGHLIGHTS XIST prevents escape of genes with DNA hypomethylated promoters in B cells. XIST maintains X-inactivation through continuous deacetylation of H3K27ac. XIST ChIRP-MS and allelic CRISPRi screen reveal a B cell-specific XIST cofactor TRIM28. XIST loss and TLR7 stimulation promotes CD11c+ atypical B cell formation." @default.
• W3119472332 created "2021-01-18" @default.
• W3119472332 creator A5025510640 @default.
• W3119472332 creator A5026885327 @default.
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• W3119472332 creator A5040230088 @default.
• W3119472332 creator A5075921949 @default.
• W3119472332 creator A5081675173 @default.
• W3119472332 date "2021-01-04" @default.
• W3119472332 modified "2023-09-23" @default.
• W3119472332 title "B cell-specific XIST complex enforces X-inactivation and restrains atypical B cells" @default.
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• W3119472332 doi "https://doi.org/10.1101/2021.01.03.425167" @default.
• W3119472332 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7805439" @default.
• W3119472332 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33442682" @default.
• W3119472332 hasPublicationYear "2021" @default.
• W3119472332 type Work @default.

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