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X-chromosome inactivation: molecular mechanisms from the human perspective

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Abstract

X-chromosome inactivation is an epigenetic process whereby one X chromosome is silenced in mammalian female cells. Since it was first proposed by Lyon in 1961, mouse models have been valuable tools to uncover the molecular mechanisms underlying X inactivation. However, there are also inherent differences between mouse and human X inactivation, ranging from sequence content of the X inactivation center to the phenotypic outcomes of X-chromosome abnormalities. X-linked gene dosage in males, females, and individuals with X aneuploidies and X/autosome translocations has demonstrated that many human genes escape X inactivation, implicating cis-regulatory elements in the spread of silencing. We discuss the potential nature of these elements and also review the elements in the X inactivation center involved in the early events in X-chromosome inactivation.

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Acknowledgments

Funding was provided by Canadian Institutes of Health Research (MOP-13690).

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Authors and Affiliations

  1. Department of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada

    Christine Yang, Andrew G. Chapman, Angela D. Kelsey, Jakub Minks, Allison M. Cotton & Carolyn J. Brown

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  1. Christine Yang
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  2. Andrew G. Chapman
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  3. Angela D. Kelsey
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Correspondence to Carolyn J. Brown.

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Yang, C., Chapman, A.G., Kelsey, A.D. et al. X-chromosome inactivation: molecular mechanisms from the human perspective. Hum Genet 130, 175–185 (2011). https://doi.org/10.1007/s00439-011-0994-9

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