X-chromosome inactivation: molecular mechanisms from the human perspective

Hum Genet. 2011 Aug;130(2):175-85. doi: 10.1007/s00439-011-0994-9. Epub 2011 May 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aneuploidy*
  • Animals
  • Epigenesis, Genetic / genetics
  • Epigenesis, Genetic / physiology*
  • Female
  • Gene Dosage / genetics
  • Gene Dosage / physiology*
  • Gene Silencing*
  • Humans
  • Male
  • Mice
  • Phenotype*
  • Translocation, Genetic / genetics*
  • X Chromosome Inactivation / genetics
  • X Chromosome Inactivation / physiology*