Erosion of human X chromosome inactivation causes major remodeling of the iPSC proteome.
Cell Rep
; 35(4): 109032, 2021 04 27.
Article
em En
| MEDLINE
| ID: mdl-33910018
ABSTRACT
X chromosome inactivation (XCI) is a dosage compensation mechanism in female mammals whereby transcription from one X chromosome is repressed. Analysis of human induced pluripotent stem cells (iPSCs) derived from female donors identified that low levels of XIST RNA correlated strongly with erosion of XCI. Proteomic analysis, RNA sequencing (RNA-seq), and polysome profiling showed that XCI erosion resulted in amplified RNA and protein expression from X-linked genes, providing a proteomic characterization of skewed dosage compensation. Increased protein expression was also detected from autosomal genes without an mRNA increase, thus altering the protein-RNA correlation between the X chromosome and autosomes. XCI-eroded lines display an â¼13% increase in total cell protein content, with increased ribosomal proteins, ribosome biogenesis and translation factors, and polysome levels. We conclude that XCI erosion in iPSCs causes a remodeling of the proteome, affecting the expression of a much wider range of proteins and disease-linked loci than previously realized.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteoma
/
Inativação do Cromossomo X
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Células-Tronco Pluripotentes Induzidas
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Female
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Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2021
Tipo de documento:
Article