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Genes that escape from X inactivation

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Abstract

To achieve a balanced gene expression dosage between males (XY) and females (XX), mammals have evolved a compensatory mechanism to randomly inactivate one of the female X chromosomes. Despite this chromosome-wide silencing, a number of genes escape X inactivation: in women about 15% of X-linked genes are bi-allelically expressed and in mice, about 3%. Expression from the inactive X allele varies from a few percent of that from the active allele to near equal expression. While most genes have a stable inactivation pattern, a subset of genes exhibit tissue-specific differences in escape from X inactivation. Escape genes appear to be protected from the repressive chromatin modifications associated with X inactivation. Differences in the identity and distribution of escape genes between species and tissues suggest a role for these genes in the evolution of sex differences in specific phenotypes. The higher expression of escape genes in females than in males implies that they may have female-specific roles and may be responsible for some of the phenotypes observed in X aneuploidy.

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Acknowledgments

This work was supported by grants from the National Institutes of Health to J. B. B. (HD060402), C. M. D. (GM046883 and GM079537), L. C. (HD056452) and J. X. (MH083949).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, University of Washington School of Medicine, Seattle, WA, 98195, USA

    Joel B. Berletch, Fan Yang & Christine M. Disteche

  2. Department of Medicine, University of Washington School of Medicine, Seattle, WA, 98195, USA

    Christine M. Disteche

  3. Department of Biomedical Sciences, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA, 01536, USA

    Jun Xu

  4. Department of Biochemistry and Molecular Biology, Pennsylvania State College of Medicine, Hershey, PA, 17033, USA

    Laura Carrel

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  1. Joel B. Berletch
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  2. Fan Yang
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  3. Jun Xu
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  4. Laura Carrel
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  5. Christine M. Disteche
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Correspondence to Christine M. Disteche.

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Berletch, J.B., Yang, F., Xu, J. et al. Genes that escape from X inactivation. Hum Genet 130, 237–245 (2011). https://doi.org/10.1007/s00439-011-1011-z

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