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dc.contributor.authorMazzarella, L
dc.contributor.authorJørgensen, H
dc.contributor.authorSoza-Ried, J
dc.contributor.authorTerry, A
dc.contributor.authorPearson, Stella
dc.contributor.authorLacaud, Georges
dc.contributor.authorKouskoff, Valerie
dc.contributor.authorMerkenschlager, M
dc.contributor.authorFisher, A
dc.date.accessioned2011-12-02T15:18:47Z
dc.date.available2011-12-02T15:18:47Z
dc.date.issued2011-01-06
dc.identifier.citationEmbryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression. 2011, 117 (1):83-7 Blooden
dc.identifier.issn1528-0020
dc.identifier.pmid20876850
dc.identifier.doi10.1182/blood-2010-03-273128
dc.identifier.urihttp://hdl.handle.net/10541/192871
dc.description.abstractMany lineage-specific developmental regulator genes are transcriptionally primed in embryonic stem (ES) cells; RNA Pol(II) is bound at their promoters but is prevented from productive elongation by the activity of polycomb repressive complexes (PRC) 1 and 2. This epigenetically poised state is thought to enable ES cells to rapidly execute multiple differentiation programs and is recognized by a simultaneous enrichment for trimethylation of lysine 4 and trimethylation of lysine 27 of histone H3 (bivalent chromatin) across promoter regions. Here we show that the chromatin profile of this important cohort of genes is progressively modified as ES cells differentiate toward blood-forming precursors. Surprisingly however, neural specifying genes, such as Nkx2-2, Nkx2-9, and Sox1, remain bivalent and primed even in committed hemangioblasts, as conditional deletion of PRC1 results in overt and inappropriate expression of neural genes in hemangioblasts. These data reinforce the importance of PRC1 for normal hematopoietic differentiation and reveal an unexpected epigenetic plasticity of mesoderm-committed hemangioblasts.
dc.language.isoenen
dc.subject.meshAnimals
dc.subject.meshBlotting, Western
dc.subject.meshCell Differentiation
dc.subject.meshCells, Cultured
dc.subject.meshChromatin
dc.subject.meshChromatin Immunoprecipitation
dc.subject.meshDNA-Binding Proteins
dc.subject.meshEmbryonic Stem Cells
dc.subject.meshEpigenesis, Genetic
dc.subject.meshFetal Proteins
dc.subject.meshGreen Fluorescent Proteins
dc.subject.meshHemangioblasts
dc.subject.meshHistones
dc.subject.meshHomeodomain Proteins
dc.subject.meshIntegrases
dc.subject.meshMice
dc.subject.meshMice, Knockout
dc.subject.meshRNA, Messenger
dc.subject.meshRepressor Proteins
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction
dc.subject.meshSOXB1 Transcription Factors
dc.subject.meshT-Box Domain Proteins
dc.subject.meshTranscription Factors
dc.subject.meshVascular Endothelial Growth Factor Receptor-2
dc.titleEmbryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression.en
dc.typeArticleen
dc.contributor.departmentLymphocyte Development Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, London, United Kingdom.en
dc.identifier.journalBlooden
html.description.abstractMany lineage-specific developmental regulator genes are transcriptionally primed in embryonic stem (ES) cells; RNA Pol(II) is bound at their promoters but is prevented from productive elongation by the activity of polycomb repressive complexes (PRC) 1 and 2. This epigenetically poised state is thought to enable ES cells to rapidly execute multiple differentiation programs and is recognized by a simultaneous enrichment for trimethylation of lysine 4 and trimethylation of lysine 27 of histone H3 (bivalent chromatin) across promoter regions. Here we show that the chromatin profile of this important cohort of genes is progressively modified as ES cells differentiate toward blood-forming precursors. Surprisingly however, neural specifying genes, such as Nkx2-2, Nkx2-9, and Sox1, remain bivalent and primed even in committed hemangioblasts, as conditional deletion of PRC1 results in overt and inappropriate expression of neural genes in hemangioblasts. These data reinforce the importance of PRC1 for normal hematopoietic differentiation and reveal an unexpected epigenetic plasticity of mesoderm-committed hemangioblasts.


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