DEAF-1, a novel protein that binds an essential region in a Deformed response element.
A 120 bp homeotic response element that is regulated specifically by Deformed in Drosophila embryos contains a single binding site for Deformed protein. However, a 24 bp sub-element containing this site does not constitute a Deformed response element. Specific activation requires a second region in the 120 bp element, which presumably contains one or more binding sites for Deformed cofactors. We have isolated a novel protein from Drosophila nuclear extracts which binds specifically to a site in this second region. This protein, which we call DEAF-1 (Deformed epidermal autoregulatory factor-1), contains three conserved domains. One of these includes a cysteine repeat motif that is similar to a motif found in Drosophila Nervy and the human MTG8 proto-oncoprotein, and another matches a region of Drosophila Trithorax. Mutations in the response element designed to improve binding to DEAF-1 in vitro resulted in increased embryonic expression. Conversely, small mutations designed to diminish binding to DEAF-1 resulted in reduced expression of the element. Thus, DEAF-1 is likely to contribute to the functional activity, and perhaps to the homeotic specificity, of this response element. Consistent with this hypothesis, we have discovered DEAF-1 binding sites in other Deformed response elements.
Gross
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Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.
McGinnis
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; C066676:Dfd protein, Drosophila; D029721:Drosophila Proteins; D018398:Homeodomain Proteins