ID | 116512 |
Author |
Brenes, Alejandro J.
University of Dundee
Yoshikawa, Harunori
University of Dundee|Tokushima University
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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
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Content Type |
Journal Article
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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.
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Journal Title |
Cell Reports
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ISSN | 22111247
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Publisher | Elsevier
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Volume | 35
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Issue | 4
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Start Page | 109032
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Published Date | 2021-04-27
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Rights | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
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language |
eng
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TextVersion |
Publisher
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departments |
Institute of Advanced Medical Sciences
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