Genetics and epigenetics of the X chromosome

Ann N Y Acad Sci. 2010 Dec;1214:E18-33. doi: 10.1111/j.1749-6632.2010.05943.x.


A consequence of Mendelian inheritance of X-linked traits is that women are more than equal to men in the face of X-linked diseases, protected as they are by the presence of two X chromosomes in their genome. This potentially beneficial inequality is diminished by the molecular mechanism known as X-chromosome inactivation (XCI), which triggers the transcriptional silencing of one of the X chromosomes in each female cell. The determination of which X to inactivate, a process that occurs during early embryogenesis, is random and clonally inherited. As a result, females are mosaic for the expression of X-linked genes. XCI is a highly regulated process involving large noncoding RNAs, chromatin remodeling, and nuclear reorganization of the X chromosome. It is a paradigm for epigenetic regulation and is frequently used as a biomarker for monitoring long-range gene reprogramming during cell differentiation and dedifferentiation. Our review analyses how XCI affects the expression of X-linked mutations, describes some of the most recent discoveries on the molecular mechanisms triggering XCI, and explores the therapeutic potentialities of the XCI process per se.

Publication types

  • Review

MeSH terms

  • Animals
  • Chromosomes, Human, X / genetics
  • Epigenesis, Genetic / genetics*
  • Female
  • Genes, X-Linked / genetics
  • Humans
  • Male
  • Sex Characteristics*
  • Sex Chromosome Aberrations*
  • X Chromosome / genetics*
  • X Chromosome Inactivation / genetics*