Role of histone H3 lysine 27 methylation in X inactivation

Science. 2003 Apr 4;300(5616):131-5. doi: 10.1126/science.1084274. Epub 2003 Mar 20.

Abstract

The Polycomb group (PcG) protein Eed is implicated in regulation of imprinted X-chromosome inactivation in extraembryonic cells but not of random X inactivation in embryonic cells. The Drosophila homolog of the Eed-Ezh2 PcG protein complex achieves gene silencing through methylation of histone H3 on lysine 27 (H3-K27), which suggests a role for H3-K27 methylation in imprinted X inactivation. Here we demonstrate that transient recruitment of the Eed-Ezh2 complex to the inactive X chromosome (Xi) occurs during initiation of X inactivation in both extraembryonic and embryonic cells and is accompanied by H3-K27 methylation. Recruitment of the complex and methylation on the Xi depend on Xist RNA but are independent of its silencing function. Together, our results suggest a role for Eed-Ezh2-mediated H3-K27 methylation during initiation of both imprinted and random X inactivation and demonstrate that H3-K27 methylation is not sufficient for silencing of the Xi.

Publication types

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

MeSH terms

  • Animals
  • Blastocyst / metabolism
  • Blastocyst / physiology*
  • Cell Differentiation
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Dosage Compensation, Genetic*
  • Female
  • Fluorescent Antibody Technique
  • Genomic Imprinting
  • HeLa Cells
  • Histones / metabolism*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lysine / metabolism
  • Male
  • Methylation
  • Mice
  • Mutation
  • Polycomb Repressive Complex 2
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism
  • Repressor Proteins / metabolism
  • Stem Cells / metabolism
  • Stem Cells / physiology*
  • Transgenes
  • Trophoblasts / physiology*
  • X Chromosome / metabolism*

Substances

  • EED protein, human
  • Eed protein, mouse
  • Histones
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Repressor Proteins
  • XIST non-coding RNA
  • Polycomb Repressive Complex 2
  • Lysine