Distinct dosage compensations of ploidy-sensitive and -insensitive X chromosome genes during development and in diseases.
iScience
; 26(2): 105997, 2023 Feb 17.
Article
en En
| MEDLINE
| ID: mdl-36798435
ABSTRACT
The active X chromosome in mammals is upregulated to balance its dosage to autosomes during evolution. However, it is elusive why the known dosage compensation machinery showed uneven and small influence on X genes. Here, based on >20,000 transcriptomes, we identified two X gene groups (ploidy-sensitive [PSX] and ploidy-insensitive [PIX]), showing distinct but evolutionarily conserved dosage compensations (termed XAR). We demonstrated that XAR-PIX was downregulated whereas XAR-PSX upregulated at both RNA and protein levels across cancer types, in contrast with their trends during stem cell differentiation. XAR-PIX, but not XAR-PSX, was lower and correlated with autoantibodies and inflammation in patients of lupus, suggesting that insufficient dosage of PIX genes contribute to lupus pathogenesis. We further identified and experimentally validated two XAR regulators, TP53 and ATRX. Collectively, we provided insights into X dosage compensation in mammals and demonstrated different regulation of PSX and PIX and their pathophysiological roles in human diseases.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Revista:
IScience
Año:
2023
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA