Long-range cis effects of ectopic X-inactivation centres on a mouse autosome

Nature. 1997 Mar 20;386(6622):275-9. doi: 10.1038/386275a0.


In mammals, the X chromosome is unique in being capable of complete inactivation. Such X inactivation evolved to compensate for gene dosage differences between females with two X chromosomes and males with one. Transcriptional silencing of a single female X chromosome is controlled in cis by Xist, whose RNA product coats the inactive X chromosome (Xi), and the X-inactivation centre (Xic). A transgenic study limited the Xic to 450 kilobases including Xist, and demonstrated that it is sufficient to initiate X inactivation. Here we report that ectopic Xist RNA completely coats transgenic chromosome 12. Expression of genes over 50 centimorgans was reduced two-fold and was detected only from the normal homologue in fibroblasts. Moreover, ectopic Xic action resulted in chromosome-wide changes that are characteristic of the X(i): DNA replication was delayed, and histone H4 was markedly hypoacetylated. Our findings suggest long-range cis effects on the autosome similar to those of X inactivation, and imply that the Xic can both initiate X inactivation and drive heterochromatin formation. Thus, the potential for chromosome-wide gene regulation is not intrinsic to X-chromosome DNA, but can also occur on autosomes possessing the Xic.

Publication types

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

MeSH terms

  • Acetylation
  • Animals
  • Cell Line
  • Chromosome Mapping
  • DNA-Binding Proteins / genetics
  • Dosage Compensation, Genetic*
  • Erythroid-Specific DNA-Binding Factors
  • Female
  • Fibroblasts / cytology
  • Gene Expression
  • Genes, fos
  • Heterochromatin / metabolism
  • Histones / metabolism
  • In Situ Hybridization, Fluorescence
  • Male
  • Mice
  • Mice, Transgenic
  • Polymerase Chain Reaction
  • RNA / metabolism
  • RNA, Long Noncoding
  • RNA, Untranslated*
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • Heterochromatin
  • Histones
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Transcription Factors
  • XIST non-coding RNA
  • RNA