Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic.
The TGF-beta (transforming growth factor-beta)-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 family, which are thought to act as co-activators of transcription, perhaps in conjunction with sequence-specific cofactors. Here we show that the amino-terminal domain of the Drosophila Mothers against dpp protein (Mad), a mediator of Dpp signalling, 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.
Kim
J
J
Howard Hughes Medical Institute, University of Wisconsin, Madison 53706, USA.
Johnson
K
K
Chen
H J
HJ
Carroll
S
S
Laughon
A
A
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology / Q000235:genetics; D029721:Drosophila Proteins; D004627:Embryonic Induction; D004742:Enhancer Elements, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D015398:Signal Transduction; D014157:Transcription Factors; D014921:Wings, Animal / Q000196:embryology
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; C112506:MAD protein, Drosophila; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C066177:Ubx protein, Drosophila; C064196:dpp protein, Drosophila; C059843:lab protein, Drosophila; C095064:vg protein, Drosophila; D004247:DNA