Xist RNA and the mechanism of X chromosome inactivation

Annu Rev Genet. 2002:36:233-78. doi: 10.1146/annurev.genet.36.042902.092433. Epub 2002 Jun 11.


Dosage compensation in mammals is achieved by the transcriptional inactivation of one X chromosome in female cells. From the time X chromosome inactivation was initially described, it was clear that several mechanisms must be precisely integrated to achieve correct regulation of this complex process. X-inactivation appears to be triggered upon differentiation, suggesting its regulation by developmental cues. Whereas any number of X chromosomes greater than one is silenced, only one X chromosome remains active. Silencing on the inactive X chromosome coincides with the acquisition of a multitude of chromatin modifications, resulting in the formation of extraordinarily stable facultative heterochromatin that is faithfully propagated through subsequent cell divisions. The integration of all these processes requires a region of the X chromosome known as the X-inactivation center, which contains the Xist gene and its cis-regulatory elements. Xist encodes an RNA molecule that plays critical roles in the choice of which X chromosome remains active, and in the initial spread and establishment of silencing on the inactive X chromosome. We are now on the threshold of discovering the factors that regulate and interact with Xist to control X-inactivation, and closer to an understanding of the molecular mechanisms that underlie this complex process.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Chromatin / genetics
  • Dosage Compensation, Genetic*
  • Gene Silencing
  • Mice
  • RNA / genetics*
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics*


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