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ID 116512
Author
Brenes, Alejandro J. University of Dundee
Bensaddek, Dalila University of Dundee|King Abdullah University of Science and Technology
Mirauta, Bogdan European Molecular Biology Laboratory
Seaton, Daniel European Molecular Biology Laboratory
Hukelmann, Jens L. University of Dundee|Immatics Biotechnologies
Jiang, Hao University of Dundee
Stegle, Oliver European Molecular Biology Laboratory|German Cancer Research Center
Lamond, Angus I. University of Dundee
Content Type
Journal Article
Description
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 ∼13% 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.
Journal Title
Cell Reports
ISSN
22111247
Publisher
Elsevier
Volume
35
Issue
4
Start Page
109032
Published Date
2021-04-27
Rights
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences