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

TitleThe NuRD component Mbd3 is required for pluripotency of embryonic stem cells.
Publication TypeJournal Article
Year of Publication2006
AuthorsKaji K, Caballero IMartín, MacLeod R, Nichols J, Wilson V, Hendrich B
JournalNat Cell Biol
Volume8
Issue3
Pagination285-92
Date Published2006 Mar
ISSN1465-7392
KeywordsAnimals, Cell Differentiation, Cell Lineage, Cells, Cultured, DNA-Binding Proteins, Embryo, Mammalian, Epigenesis, Genetic, Gene Silencing, Histone Deacetylases, Interleukin-6, Leukemia Inhibitory Factor, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Mice, Pluripotent Stem Cells, Transcription Factors
Abstract

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.

DOI10.1038/ncb1372
Alternate JournalNat. Cell Biol.
PubMed ID16462733
Grant List064623 / / Wellcome Trust / United Kingdom
073621 / / Wellcome Trust / United Kingdom
G0300058 / / Medical Research Council / United Kingdom
G9806702 / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom