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dc.contributor.authorBode, D
dc.contributor.authorYu, L
dc.contributor.authorTate, P
dc.contributor.authorPardo, M
dc.contributor.authorChoudhary, J
dc.date.accessioned2020-06-22T15:47:44Z
dc.date.issued2016-03-01
dc.identifier.citationMolecular & cellular proteomics : MCP, 2016, 15 (3), pp. 878 - 891
dc.identifier.issn1535-9476
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3768
dc.identifier.eissn1535-9484
dc.identifier.doi10.1074/mcp.m115.053207
dc.description.abstractPluripotency and self-renewal, the defining properties of embryonic stem cells, are brought about by transcriptional programs involving an intricate network of transcription factors and chromatin remodeling complexes. The Nucleosome Remodeling and Deacetylase (NuRD) complex plays a crucial and dynamic role in the regulation of stemness and differentiation. Several NuRD-associated factors have been reported but how they are organized has not been investigated in detail. Here, we have combined affinity purification and blue native polyacrylamide gel electrophoresis followed by protein identification by mass spectrometry and protein correlation profiling to characterize the topology of the NuRD complex. Our data show that in mouse embryonic stem cells the NuRD complex is present as two distinct assemblies of differing topology with different binding partners. Cell cycle regulator Cdk2ap1 and transcription factor Sall4 associate only with the higher mass NuRD assembly. We further establish that only isoform Sall4a, and not Sall4b, associates with NuRD. By contrast, Suz12, a component of the PRC2 Polycomb repressor complex, associates with the lower mass entity. In addition, we identify and validate a novel NuRD-associated protein, Wdr5, a regulatory subunit of the MLL histone methyltransferase complex, which associates with both NuRD entities. Bioinformatic analyses of published target gene sets of these chromatin binding proteins are in agreement with these structural observations. In summary, this study provides an interesting insight into mechanistic aspects of NuRD function in stem cell biology. The relevance of our work has broader implications because of the ubiquitous nature of the NuRD complex. The strategy described here can be more broadly applicable to investigate the topology of the multiple complexes an individual protein can participate in.
dc.formatPrint-Electronic
dc.format.extent878 - 891
dc.languageeng
dc.language.isoeng
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectNucleosomes
dc.subjectAnimals
dc.subjectMice
dc.subjectProtein Kinases
dc.subjectIntracellular Signaling Peptides and Proteins
dc.subjectProteins
dc.subjectDNA-Binding Proteins
dc.subjectTumor Suppressor Proteins
dc.subjectTranscription Factors
dc.subjectChromatin Assembly and Disassembly
dc.subjectProtein Binding
dc.subjectMass Spectrometry
dc.subjectMi-2 Nucleosome Remodeling and Deacetylase Complex
dc.subjectPolycomb Repressive Complex 2
dc.subjectNative Polyacrylamide Gel Electrophoresis
dc.subjectMouse Embryonic Stem Cells
dc.titleCharacterization of Two Distinct Nucleosome Remodeling and Deacetylase (NuRD) Complex Assemblies in Embryonic Stem Cells.
dc.typeJournal Article
rioxxterms.versionofrecord10.1074/mcp.m115.053207
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfMolecular & cellular proteomics : MCP
pubs.issue3
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Functional Proteomics Group
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Functional Proteomics Group
pubs.publication-statusPublished
pubs.volume15
pubs.embargo.termsNot known
icr.researchteamFunctional Proteomics Group
dc.contributor.icrauthorPardo Calvo, Maria Mercedes
dc.contributor.icrauthorChoudhary, Jyoti


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