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U-shaped protein domains required for repression of cardiac gene expression in Drosophila

Authors

  • Tsuyoshi Tokusumi,

    1. Department of Biochemistry and Molecular Biology, Program in Genes & Development, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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  • Mark Russell,

    1. Department of Biochemistry and Molecular Biology, Program in Genes & Development, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
      Tel: +1 713 834 6293
      Fax: +1 713 834 6291
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  • Kathleen Gajewski,

    1. Department of Biochemistry and Molecular Biology, Program in Genes & Development, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
      Tel: +1 713 834 6293
      Fax: +1 713 834 6291
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  • Nancy Fossett,

    1. Department of Pathology, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, 800 W. Baltimore Street, Baltimore, MD 21201, USA
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  • Robert A. Schulz

    Corresponding author
    1. Department of Biochemistry and Molecular Biology, Program in Genes & Development, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
      Tel: +1 713 834 6293
      Fax: +1 713 834 6291
    Search for more papers by this author

✉ E-mail: raschulz@mdanderson.org

Abstract

Abstract U-shaped is a zinc finger protein that functions predominantly as a negative transcriptional regulator of cell fate determination during Drosophila development. In the early stages of dorsal vessel formation, the protein acts to control cardioblast specification, working as a negative attenuator of the cardiogenic GATA factor Pannier. Pannier and the homeodomain protein Tinman normally work together to specify heart cells and activate cardioblast gene expression. One target of this positive regulation is a heart enhancer of the D-mef2 gene and U-shaped has been shown to antagonize enhancer activation by Pannier and Tinman. We have mapped protein domains of U-shaped required for its repression of cardioblast gene expression. Such studies showed GATA factor interacting zinc fingers of U-shaped are required for enhancer repression, as well as three small motifs that are likely needed for co-factor binding and/or protein modification. These analyses have also allowed for the definition of a 253 amino acid interval of U-shaped that is essential for its nuclear localization. Together, these findings provide molecular insights into the function of U-shaped as a negative regulator of heart development in Drosophila.

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