An Xist-activating antisense RNA required for X-chromosome inactivation

Nat Commun. 2015 Oct 19:6:8564. doi: 10.1038/ncomms9564.

Abstract

The transcriptional imbalance due to the difference in the number of X chromosomes between male and female mammals is remedied through X-chromosome inactivation, the epigenetic transcriptional silencing of one of the two X chromosomes in females. The X-linked Xist long non-coding RNA functions as an X inactivation master regulator; Xist is selectively upregulated from the prospective inactive X chromosome and is required in cis for X inactivation. Here we discover an Xist antisense long non-coding RNA, XistAR (Xist Activating RNA), which is encoded within exon 1 of the mouse Xist gene and is transcribed only from the inactive X chromosome. Selective truncation of XistAR, while sparing the overlapping Xist RNA, leads to a deficiency in Xist RNA expression in cis during the initiation of X inactivation. Thus, the Xist gene carries within its coding sequence an antisense RNA that drives Xist expression.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Chromosome Mapping
  • Female
  • In Situ Hybridization, Fluorescence
  • Male
  • Mice, Inbred C57BL
  • RNA, Antisense / metabolism*
  • RNA, Long Noncoding*
  • X Chromosome Inactivation*

Substances

  • RNA, Antisense
  • RNA, Long Noncoding
  • XIST non-coding RNA