Genes That Escape From X Inactivation

Hum Genet. 2011 Aug;130(2):237-45. doi: 10.1007/s00439-011-1011-z. Epub 2011 May 26.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aneuploidy*
  • Animals
  • Biological Evolution*
  • Female
  • Gene Dosage / genetics*
  • Genes, X-Linked / genetics*
  • Humans
  • Male
  • Mice
  • Phenotype*
  • Sex Factors
  • Species Specificity
  • X Chromosome Inactivation / genetics*
  • X Chromosome Inactivation / physiology