title: NuRD-mediated deacetylation of H3K27 facilitates recruitment of Polycomb Repressive Complex 2 to direct gene repression.
abstract: Pluripotent cells possess the ability to differentiate into any cell type. Commitment to differentiate into specific lineages requires strict control of gene expression to coordinate the downregulation of lineage inappropriate genes while enabling the expression of lineage-specific genes. The nucleosome remodelling and deacetylation complex (NuRD) is required for lineage commitment of pluripotent cells; however, the mechanism through which it exerts this effect has not been defined. Here, we show that histone deacetylation by NuRD specifies recruitment for Polycomb Repressive Complex 2 (PRC2) in embryonic stem (ES) cells. NuRD-mediated deacetylation of histone H3K27 enables PRC2 recruitment and subsequent H3K27 trimethylation at NuRD target promoters. We propose a gene-specific mechanism for modulating expression of transcriptionally poised genes whereby NuRD controls the balance between acetylation and methylation of histones, thereby precisely directing the expression of genes critical for embryonic development.
authors.affiliation: Wellcome Trust Centre for Stem Cell Research and MRC Centre for Stem Cell Biology and Regenerative Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Reynolds
authors.forename: Mali
authors.initials: M
authors.lastname: Salmon-Divon
authors.forename: Heidi
authors.initials: H
authors.lastname: Dvinge
authors.forename: Antony
authors.initials: A
authors.lastname: Hynes-Allen
authors.forename: Gayan
authors.initials: G
authors.lastname: Balasooriya
authors.forename: Donna
authors.initials: D
authors.lastname: Leaford
authors.forename: Axel
authors.initials: A
authors.lastname: Behrens
authors.forename: Paul
authors.initials: P
authors.lastname: Bertone
authors.forename: Brian
authors.initials: B
authors.lastname: Hendrich
mesh_terms: D000107:Acetylation; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism*; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D063146:Polycomb-Group Proteins; D011485:Protein Binding; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D006657:Histones; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex