Abstract
Purpose of Review
In multicellular organisms, development of genetic sex determination leads to gene dosage imbalances between the sex chromosomes and the autosomes and between the sexes. In mammals with XY-based system, a dosage compensation mechanism called X chromosome inactivation (XCI) balances gene expression from unequal number of sex chromosomes between the homogametic (XX) females and heterogametic (XY) males. XCI-mediated dosage compensation involves transcriptional silencing of one of the two X chromosomes in female cells and is tightly mediated during early development.
Recent Findings
The silencing mechanism relies on coordinated action of several epigenetic mechanisms that include imprinting, long noncoding RNA (lncRNA)-mediated chromatin regulation, and nuclear organization. Alterations in the establishment and maintenance of XCI have been associated with female-specific developmental defects, X-linked diseases, and cancer.
Summary
In this review, we discuss the current understanding on the epigenetic and lncRNA-mediated regulation of XCI and how alterations in XCI are linked to developmental defects and diseases such as cancer.
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References
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Acknowledgements
We thank all the members of the Yildirim lab for helpful discussions. This work was support by Leukemia Research Foundation Award (E.Y), Whitehead Research Fellowship (E.Y.), and Duke University Medical School Department of Cell Biology Startup Funds (E.Y.).
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Tianqi Yang and Eda Yildirim declare that they have no conflict of interest.
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Yang, T., Yildirim, E. Epigenetic and LncRNA-Mediated Regulation of X Chromosome Inactivation and Its Impact on Pathogenesis. Curr Pathobiol Rep 5, 1–12 (2017). https://doi.org/10.1007/s40139-017-0120-3
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DOI: https://doi.org/10.1007/s40139-017-0120-3