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    The histone acetyl transferase activity of monocytic leukemia zinc finger is critical for the proliferation of hematopoietic precursors.

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    Authors
    Perez-Campo, Flor-Maria
    Borrow, Julian
    Kouskoff, Valerie
    Lacaud, Georges
    Affiliation
    Paterson Institute for Cancer Research, University of Manchester, USA.
    Issue Date
    2009-05-14
    
    Metadata
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    Abstract
    The monocytic leukemia zinc finger (MOZ) gene encodes a large multidomain protein that contains, besides other domains, 2 coactivation domains for the transcription factor Runx1/acute myeloid leukemia 1 and a histone acetyl transferase (HAT) catalytic domain. Recent studies have demonstrated the critical requirement for the complete MOZ protein in hematopoietic stem cell development and maintenance. However, the specific function of the HAT activity of MOZ remains unknown, as it has been shown that MOZ HAT activity is not required either for its role as Runx1 coactivator or for the leukemic transformation induced by MOZ transcriptional intermediary factor 2 (TIF2). To assess the specific requirement for this HAT activity during hematopoietic development, we have generated embryonic stem cells and mouse lines carrying a point mutation that renders the protein catalytically inactive. We report in this study that mice exclusively lacking the HAT activity of MOZ exhibit significant defects in the number of hematopoietic stem cells and hematopoietic committed precursors as well as a defect in B-cell development. Furthermore, we demonstrate that the failure to maintain a normal number of hematopoietic precursors is caused by the inability of HAT(-/-) cells to expand. These results indicate a specific role of MOZ-driven acetylation in controlling a desirable balance between proliferation and differentiation during hematopoiesis.
    Citation
    The histone acetyl transferase activity of monocytic leukemia zinc finger is critical for the proliferation of hematopoietic precursors. 2009, 113 (20):4866-74 Blood
    Journal
    Blood
    URI
    http://hdl.handle.net/10541/74014
    DOI
    10.1182/blood-2008-04-152017
    PubMed ID
    19264921
    Type
    Article
    Language
    en
    ISSN
    1528-0020
    ae974a485f413a2113503eed53cd6c53
    10.1182/blood-2008-04-152017
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research
    Stem Cell and Haematopoiesis
    Stem Cell Biology

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