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    Embryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression.

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    Authors
    Mazzarella, L
    Jørgensen, H
    Soza-Ried, J
    Terry, A
    Pearson, Stella
    Lacaud, Georges
    Kouskoff, Valerie
    Merkenschlager, M
    Fisher, A
    Affiliation
    Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, London, United Kingdom.
    Issue Date
    2011-01-06
    
    Metadata
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    Abstract
    Many 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.
    Citation
    Embryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression. 2011, 117 (1):83-7 Blood
    Journal
    Blood
    URI
    http://hdl.handle.net/10541/192871
    DOI
    10.1182/blood-2010-03-273128
    PubMed ID
    20876850
    Type
    Article
    Language
    en
    ISSN
    1528-0020
    ae974a485f413a2113503eed53cd6c53
    10.1182/blood-2010-03-273128
    Scopus Count
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    All Paterson Institute for Cancer Research

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