X-inactivation profile reveals extensive variability in X-linked gene expression in females

Nature. 2005 Mar 17;434(7031):400-4. doi: 10.1038/nature03479.


In female mammals, most genes on one X chromosome are silenced as a result of X-chromosome inactivation. However, some genes escape X-inactivation and are expressed from both the active and inactive X chromosome. Such genes are potential contributors to sexually dimorphic traits, to phenotypic variability among females heterozygous for X-linked conditions, and to clinical abnormalities in patients with abnormal X chromosomes. Here, we present a comprehensive X-inactivation profile of the human X chromosome, representing an estimated 95% of assayable genes in fibroblast-based test systems. In total, about 15% of X-linked genes escape inactivation to some degree, and the proportion of genes escaping inactivation differs dramatically between different regions of the X chromosome, reflecting the evolutionary history of the sex chromosomes. An additional 10% of X-linked genes show variable patterns of inactivation and are expressed to different extents from some inactive X chromosomes. This suggests a remarkable and previously unsuspected degree of expression heterogeneity among females.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Chromosomes, Human, X / genetics*
  • Chromosomes, Human, Y / genetics*
  • CpG Islands / genetics
  • Dosage Compensation, Genetic*
  • Female
  • Fibroblasts
  • Gene Expression Profiling*
  • Gene Expression Regulation / genetics*
  • Heterozygote
  • Humans
  • Male
  • Phenotype
  • RNA, Long Noncoding
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • RNA, Untranslated / genetics
  • Sex Characteristics*
  • Transcription, Genetic / genetics


  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA, Untranslated
  • XIST non-coding RNA