Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic
Jaeseob Kim,
Kirby Johnson,
Hui Ju Chen,
Sean Carroll and
Allen Laughon ()
Additional contact information
Jaeseob Kim: *Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin
Kirby Johnson: 445 Henry Mall, University of Wisconsin-Madison
Hui Ju Chen: McArdle Laboratory, University of Wisconsin-Madison
Sean Carroll: *Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin
Allen Laughon: Correspondence and requests for materials should be addressed to A.L.
Nature, 1997, vol. 388, issue 6639, 304-308
Abstract:
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.
Date: 1997
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DOI: 10.1038/40906
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