1. ¹Harvard Medical School, Boston, Massachusetts, USA
2. ²Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA
3. ³Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA
4. ⁴MGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA

Correspondence: Dr Hensin Tsao, Department of Dermatology, Harvard Medical School, Bartlett 622, 50 Blossom Street, Boston, MA 02114, USA. E-mail: htsao@partners.org

Received 28 September 2007; Revised 2 April 2008; Accepted 6 April 2008; Published online 29 May 2008.

Abstract

X-chromosome inactivation (XCI) is the process in which females transcriptionally silence one of their two X chromosomes in early embryonic development, equalizing X chromosome gene expression between males and females. XCI depends on a gene called XIST, a functional RNA molecule that does not code for a protein. Recent studies indicate abundant intergenic transcription and nonprotein coding RNAs in the human genome, which are suspected to function in modulating gene expression. XCI may therefore serve as a useful model to learn and understand the potential function of these elements, as well as their effects on human disease. Here, we review the genetic and molecular basis of XCI and describe how the mechanistics of this process lead to the phenotypes of X-linked skin diseases, most notably in the pattern of lines, swirls, and whorls first noted by the dermatologist Alfred Blaschko. We suggest that XCI, and other epigenetic phenomena, will continue to impact our understanding of the genetic mechanisms of disease.