The NuRD component Mbd3 is required for pluripotency of embryonic stem cells

Nat Cell Biol. 2006 Mar;8(3):285-92. doi: 10.1038/ncb1372. Epub 2006 Feb 5.


Cells of early mammalian embryos have the potential to develop into any adult cell type, and are thus said to be pluripotent. Pluripotency is lost during embryogenesis as cells commit to specific developmental pathways. Although restriction of developmental potential is often associated with repression of inappropriate genetic programmes, the role of epigenetic silencing during early lineage commitment remains undefined. Here, we used mouse embryonic stem cells to study the function of epigenetic silencing in pluripotent cells. Embryonic stem cells lacking Mbd3 - a component of the nucleosome remodelling and histone deacetylation (NuRD) complex - were viable but failed to completely silence genes that are expressed before implantation of the embryo. Mbd3-deficient embryonic stem cells could be maintained in the absence of leukaemia inhibitory factor (LIF) and could initiate differentiation in embryoid bodies or chimeric embryos, but failed to commit to developmental lineages. Our findings define a role for epigenetic silencing in the cell-fate commitment of pluripotent cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Embryo, Mammalian / cytology
  • Epigenesis, Genetic
  • Gene Silencing
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Interleukin-6 / physiology
  • Leukemia Inhibitory Factor
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex
  • Mice
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Interleukin-6
  • Leukemia Inhibitory Factor
  • Lif protein, mouse
  • Mbd3 protein, mouse
  • Transcription Factors
  • Histone Deacetylases
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex