Impacts of X-chromosome Inactivation on Cell Function

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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