Effect of TSIX disruption on XIST expression in male ES cells

Cytogenet Genome Res. 2002;99(1-4):115-8. doi: 10.1159/000071582.

Abstract

XIST and its antisense partner, TSIX, encode non-coding RNAs and play key roles in X chromosome inactivation. Targeted disruption of TSIX causes ectopic expression of XIST in the extraembryonic tissues upon maternal transmission, which subsequently results in embryonic lethality due to inactivation of both X chromosomes in females and a single X chromosome in males. TSIX, therefore, plays a crucial role in maintaining the silenced state of XIST in CIS and regulates the imprinted X inactivation in the extraembryonic tissues. In this study, we examined the effect of TSIX disruption on XIST expression in the embryonic lineage using embryonic stem (ES) cells as a model system. Upon differentiation, XIST is ectopically activated in a subset of the nuclei of male ES cells harboring the TSIX-deficient X chromosome. Such ectopic expression, however, eventually ceased during prolonged culture. It is likely that surveillance by the X chromosome counting mechanism somehow shuts off the ectopic expression of XIST before inactivation of the X chromosome.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism*
  • Gene Expression Regulation
  • In Situ Hybridization, Fluorescence / methods
  • Male
  • Mice
  • Mutation
  • RNA / genetics
  • RNA / metabolism
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription Factors / genetics*

Substances

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