Erosion of Human X Chromosome Inactivation Causes Major Remodeling of the IPSC Proteome

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2021 Apr 28

PMID 33910018

Citations 22

Authors

Alejandro J Brenes

Harunori Yoshikawa

Dalila Bensaddek

Bogdan Mirauta

Daniel Seaton

Jens L Hukelmann

Hao Jiang

Oliver Stegle

Angus I Lamond

Affiliations

Soon will be listed here.

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 ∼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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