Impacts of X-chromosome Inactivation on Cell Function

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 2212

Special Issue Editors


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Guest Editor
CNRS-UMR 7216, Epigenetics and Cell fate, Université Paris-Cité, 75013 Paris, France
Interests: X-inactivation; non-coding genome; pluripotent stem cells; epigenetics; development; evolution

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Guest Editor
Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, China
Interests: embryonic stem cells; MEK/ERK signaling; genome stability; X chromosome inactivation; preimplantation development

Special Issue Information

Dear Colleagues,

In humans, the sexual genotype impacts both the risk of developing specific diseases and their manifestations. These sex-associated biases are notably observed for conditions affecting neural and immune cells, including certain neurodegenerative diseases, infectious diseases, and auto-immune diseases. More generally, non-reproductive cancers are also less predominant in females than in males, suggesting that female cells are somehow more resistant to the transformation process.

The contribution of sex chromosomes to these biases, and notably that of the X chromosome, which bears many genes implicated in neural and immune functions, has been long overlooked. In female mammals, the X-chromosome is subject to a specific regulation known as X-chromosome inactivation (XCI), which consists of the transcriptional silencing of one of the two X-chromosomes, thereby equalizing the dosage of X-linked gene products between the sexes. This chromosome-wide repression is established during early female development and is maintained in adult cells. Variability in XCI maintenance between cell types has, however, been suggested, and some genes escape from XCI with extensive heterogeneity across tissues.

This Special Issue aims to highlight recent findings regarding how the regulation of XCI and X-linked genes in general impacts the function of specific cell types, how it may contribute to female specificities in terms of disease development, and how the long-range silencing property of XCI may be turned into a therapeutic asset. Original research papers or reviews focusing on specific aspects of this topic, including the link between XCI and cancer development, resistance to infectious diseases, or autoimmunity, are welcome.

Dr. Céline Morey
Prof. Dr. Lingyi Chen
Guest Editors

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Keywords

  • X-inactivation
  • sex-biases
  • cell differentiation
  • autoimmunity
  • cancer

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Published Papers (1 paper)

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Research

18 pages, 5292 KiB  
Article
Establishing the Link between X-Chromosome Aberrations and TP53 Status, with Breast Cancer Patient Outcomes
by Franco Caramia, Terence P. Speed, Hui Shen, Ygal Haupt and Sue Haupt
Cells 2023, 12(18), 2245; https://doi.org/10.3390/cells12182245 - 11 Sep 2023
Cited by 2 | Viewed by 1896
Abstract
Ubiquitous to normal female human somatic cells, X-chromosome inactivation (XCI) tightly regulates the transcriptional silencing of a single X chromosome from each pair. Some genes escape XCI, including crucial tumour suppressors. Cancer susceptibility can be influenced by the variability in the genes that [...] Read more.
Ubiquitous to normal female human somatic cells, X-chromosome inactivation (XCI) tightly regulates the transcriptional silencing of a single X chromosome from each pair. Some genes escape XCI, including crucial tumour suppressors. Cancer susceptibility can be influenced by the variability in the genes that escape XCI. The mechanisms of XCI dysregulation remain poorly understood in complex diseases, including cancer. Using publicly available breast cancer next-generation sequencing data, we show that the status of the major tumour suppressor TP53 from Chromosome 17 is highly associated with the genomic integrity of the inactive X (Xi) and the active X (Xa) chromosomes. Our quantification of XCI and XCI escape demonstrates that aberrant XCI is linked to poor survival. We derived prognostic gene expression signatures associated with either large deletions of Xi; large amplifications of Xa; or abnormal X-methylation. Our findings expose a novel insight into female cancer risks, beyond those associated with the standard molecular subtypes. Full article
(This article belongs to the Special Issue Impacts of X-chromosome Inactivation on Cell Function)
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