X chromosome regulation: diverse patterns in development, tissues and disease

Nat Rev Genet. 2014 Jun;15(6):367-78. doi: 10.1038/nrg3687. Epub 2014 Apr 15.


Genes on the mammalian X chromosome are present in one copy in males and two copies in females. The complex mechanisms that regulate the X chromosome lead to evolutionary and physiological variability in gene expression between species, the sexes, individuals, developmental stages, tissues and cell types. In early development, delayed and incomplete X chromosome inactivation (XCI) in some species causes variability in gene expression. Additional diversity stems from escape from XCI and from mosaicism or XCI skewing in females. This causes sex-specific differences that manifest as differential gene expression and associated phenotypes. Furthermore, the complexity and diversity of X dosage regulation affect the severity of diseases caused by X-linked mutations.

Publication types

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

MeSH terms

  • Animals
  • Chromosome Disorders* / genetics
  • Chromosome Disorders* / metabolism
  • Chromosomes, Human, X* / genetics
  • Chromosomes, Human, X* / metabolism
  • Female
  • Gene Expression Regulation*
  • Genetic Diseases, X-Linked* / genetics
  • Genetic Diseases, X-Linked* / metabolism
  • Humans
  • Male
  • Mosaicism
  • Sex Characteristics*
  • X Chromosome Inactivation*

Supplementary concepts

  • Mosaic variegated aneuploidy syndrome