X chromosomes alternate between two states prior to random X-inactivation

PLoS Biol. 2006 Jun;4(6):e159. doi: 10.1371/journal.pbio.0040159. Epub 2006 May 9.


Early in the development of female mammals, one of the two X chromosomes is silenced in half of cells and the other X chromosome is silenced in the remaining half. The basis of this apparent randomness is not understood. We show that before X-inactivation, the two X chromosomes appear to exist in distinct states that correspond to their fates as the active and inactive X chromosomes. Xist and Tsix, noncoding RNAs that control X chromosome fates upon X-inactivation, also determine the states of the X chromosomes prior to X-inactivation. In wild-type ES cells, X chromosomes switch between states; among the progeny of a single cell, a given X chromosome exhibits each state with equal frequency. We propose a model in which the concerted switching of homologous X chromosomes between mutually exclusive future active and future inactive states provides the basis for the apparently random silencing of one X chromosome in female cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • DNA Replication
  • Female
  • In Situ Hybridization, Fluorescence
  • Mice
  • Models, Genetic
  • RNA, Long Noncoding
  • RNA, Untranslated / physiology
  • Stem Cells / cytology
  • X Chromosome / genetics*
  • X Chromosome / metabolism
  • X Chromosome Inactivation / physiology*


  • RNA, Long Noncoding
  • RNA, Untranslated
  • Tsix transcript, mouse
  • XIST non-coding RNA