B cell-specific XIST complex enforces X-inactivation and restrains atypical B cells.
Cell
; 184(7): 1790-1803.e17, 2021 04 01.
Article
en En
| MEDLINE
| ID: mdl-33735607
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 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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos B
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Receptor Toll-Like 7
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Inactivación del Cromosoma X
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ARN Largo no Codificante
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COVID-19
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Lupus Eritematoso Sistémico
Límite:
Female
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Humans
Idioma:
En
Revista:
Cell
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos