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Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic

Nature volume 388, pages 304–308 (1997)Cite this article

Abstract

The TGF-β (transforming growth factor-β)-related signalling proteins, including Decapentaplegic (Dpp) in Drosophila and bone morphogenic proteins and activin in vertebrates, affect the growth and patterning of a great variety of structures. However, the mechanisms by which these ligands regulate gene expression are not understood. Activation of complexes of type I with type II receptors results in the phosphorylation and nuclear localization of members of the SMAD protein family1,2,3,4,5,6,7,8,9, which are thought to act as co-activators of transcription, perhaps in conjunction with sequence-specific cofactors10. Here we show that the amino-terminal domain of the Drosophila Mothers against dpp protein (Mad), a mediator of Dpp signalling11,12,13,14, possesses a sequence-specific DNA-binding activity that becomes apparent when carboxy-terminal residues are removed. Mad binds to and is required for the activation of an enhancer within the vestigial wing-patterning gene in cells across the entire developing wing blade. Mad also binds to Dpp-response elements in other genes. These results suggest that Dpp signalling regulates gene expression by activating Mad binding to target gene enhancers.

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Figure 1: Mad activity is required for Vg expression in the cells of the developing wing blade.
Figure 2: The binding of MadN protein to the vg quadrant enhancer is sequence specific and essential for activation in vivo.
Figure 3: The N-terminal domain of Mad protein (MadN) binds to the vg quadrant enhancer.
Figure 4: The lab endodermal and Ubx midgut enhancers contain MadN binding sites similar to those in the vg quadrant enhancer.

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Authors and Affiliations

  1. *Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin, 1525 Linden Drive, Madison, 53706, Wisconsin, USA

    Jaeseob Kim & Sean Carroll

  2. †Departments of Genetics and Medical Genetics, 445 Henry Mall, University of Wisconsin-Madison, Madison, 53706, Wisconsin, USA

    Kirby Johnson & Sean Carroll

  3. ‡Department of Oncology, McArdle Laboratory, University of Wisconsin-Madison, Madison, 53706, Wisconsin, USA

    Hui Ju Chen

  4. Correspondence and requests for materials should be addressed to A.L.,

    Allen Laughon

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  1. Jaeseob Kim
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Correspondence to Allen Laughon.

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Kim, J., Johnson, K., Chen, H. et al. Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic. Nature 388, 304–308 (1997). https://doi.org/10.1038/40906

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