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    Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development

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    Authors
    Pimanda, John E
    Ottersbach, Katrin
    Knezevic, Kathy
    Kinston, Sarah
    Chan, Wan Y I
    Wilson, Nicola K
    Landry, Josette-Renee
    Wood, Andrew D
    Kolb-Kokocinski, Anja
    Green, Anthony R
    Tannahill, David
    Lacaud, Georges
    Kouskoff, Valerie
    Göttgens, Berthold
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    Affiliation
    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom. jpimanda@unsw.edu.au
    Issue Date
    2007-11-06
    
    Metadata
    Show full item record
    Abstract
    Conservation of the vertebrate body plan has been attributed to the evolutionary stability of gene-regulatory networks (GRNs). We describe a regulatory circuit made up of Gata2, Fli1, and Scl/Tal1 and their enhancers, Gata2-3, Fli1+12, and Scl+19, that operates during specification of hematopoiesis in the mouse embryo. We show that the Fli1+12 enhancer, like the Gata2-3 and Scl+19 enhancers, targets hematopoietic stem cells (HSCs) and relies on a combination of Ets, Gata, and E-Box motifs. We show that the Gata2-3 enhancer also uses a similar cluster of motifs and that Gata2, Fli1, and Scl are expressed in embryonic day-11.5 dorsal aorta where HSCs originate and in fetal liver where they multiply. The three HSC enhancers in these tissues and in ES cell-derived hemangioblast equivalents are bound by each of these transcription factors (TFs) and form a fully connected triad that constitutes a previously undescribed example of both this network motif in mammalian development and a GRN kernel operating during the specification of a mammalian stem cell.
    Citation
    Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development. 2007, 104 (45):17692-7 Proc. Natl. Acad. Sci. U.S.A.
    Journal
    Proceedings of the National Academy of Sciences
    URI
    http://hdl.handle.net/10541/71227
    DOI
    10.1073/pnas.0707045104
    PubMed ID
    17962413
    Type
    Article
    Language
    en
    ISSN
    0027-8424
    ae974a485f413a2113503eed53cd6c53
    10.1073/pnas.0707045104
    Scopus Count
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