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    Brachyury and Related Tbx Proteins Interact with the Mixl1 Homeodomain Protein and Negatively Regulate Mixl1 Transcriptional Activity

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    Author
    Pereira, LA; Wong, MS; Lim, SM; Sides, A; Stanley, EG; Elefanty, AG
    Date
    2011-12-02
    Source Title
    PLoS One
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Stanley, Edouard; Elefanty, Andrew
    Affiliation
    Paediatrics (RCH)
    Metadata
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    Document Type
    Journal Article
    Citations
    Pereira, L. A., Wong, M. S., Lim, S. M., Sides, A., Stanley, E. G. & Elefanty, A. G. (2011). Brachyury and Related Tbx Proteins Interact with the Mixl1 Homeodomain Protein and Negatively Regulate Mixl1 Transcriptional Activity. PLOS ONE, 6 (12), https://doi.org/10.1371/journal.pone.0028394.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256888
    DOI
    10.1371/journal.pone.0028394
    Abstract
    Mixl1 is a homeodomain transcription factor required for mesoderm and endoderm patterning during mammalian embryogenesis. Despite its crucial function in development, co-factors that modulate the activity of Mixl1 remain poorly defined. Here we report that Mixl1 interacts physically and functionally with the T-box protein Brachyury and related members of the T-box family of transcription factors. Transcriptional and protein analyses demonstrated overlapping expression of Mixl1 and Brachyury during embryonic stem cell differentiation. In vitro protein interaction studies showed that the Mixl1 with Brachyury associated via their DNA-binding domains and gel shift assays revealed that the Brachyury T-box domain bound to Mixl1-DNA complexes. Furthermore, luciferase reporter experiments indicated that association of Mixl1 with Brachyury and related T-box factors inhibited the transactivating potential of Mixl1 on the Gsc and Pdgfrα promoters. Our results indicate that the activity of Mixl1 can be modulated by protein-protein interactions and that T-box factors can function as negative regulators of Mixl1 activity.

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