Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome

Science. 2008 Oct 31;322(5902):750-6. doi: 10.1126/science.1163045.

Abstract

To equalize X-chromosome dosages between the sexes, the female mammal inactivates one of her two X chromosomes. X-chromosome inactivation (XCI) is initiated by expression of Xist, a 17-kb noncoding RNA (ncRNA) that accumulates on the X in cis. Because interacting factors have not been isolated, the mechanism by which Xist induces silencing remains unknown. We discovered a 1.6-kilobase ncRNA (RepA) within Xist and identified the Polycomb complex, PRC2, as its direct target. PRC2 is initially recruited to the X by RepA RNA, with Ezh2 serving as the RNA binding subunit. The antisense Tsix RNA inhibits this interaction. RepA depletion abolishes full-length Xist induction and trimethylation on lysine 27 of histone H3 of the X. Likewise, PRC2 deficiency compromises Xist up-regulation. Therefore, RepA, together with PRC2, is required for the initiation and spread of XCI. We conclude that a ncRNA cofactor recruits Polycomb complexes to their target locus.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Chromatin Immunoprecipitation
  • Electrophoretic Mobility Shift Assay
  • Embryonic Stem Cells
  • Female
  • Fibroblasts
  • Male
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Polycomb-Group Proteins
  • Polymerase Chain Reaction
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism*
  • Repetitive Sequences, Nucleic Acid
  • Repressor Proteins / metabolism*
  • Up-Regulation
  • X Chromosome / metabolism*
  • X Chromosome Inactivation

Substances

  • Polycomb-Group Proteins
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Repressor Proteins
  • XIST non-coding RNA

Associated data

  • GENBANK/FJ361197