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The nuclear hormone receptor Ftz-F1 is a cofactor for the Drosophila homeodomain protein Ftz

Nature volume 385, pages 552–555 (1997)Cite this article

Abstract

Homeobox genes specify cell fate and positional identity in embryos throughout the animal kingdom1. Paradoxically, although each has a specific function in vivo, the in vitro DNA-binding specificities of homeodomain proteins are overlapping and relatively weak. A current model is that homeodomain proteins interact with cofactors that increase specificity in vivo2,3. Here we use a native binding site for the homeodomain protein Fushi tarazu (Ftz) to isolate Ftz-Fl, a protein of the nuclear hormone-receptor superfamily and a new Ftz cofactor. Ftz and Ftz-Fl are present in a complex in Drosophila embryos. Ftz-Fl facilitates the binding of Ftz to DNA, allowing interactions with weak-affinity sites at concentrations of Ftz that alone bind only high-affinity sites. Embryos lacking Ftz-Fl display ftz-like pair-rule cuticular defects. This phenotype is a result of abnormal ftz function because it is expressed but fails to activate downstream target genes. Cooperative interaction between homeodomain proteins and cofactors of different classes may serve as a general mechanism to increase HOX protein specificity and to broaden the range of target sites they regulate.

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Authors and Affiliations

  1. Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, New York, 10029, USA

    Yan Yu, Kai Su, Miyuki Yussa, Wei Han & Leslie Pick

  2. Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Willis Li & Norbert Perrimon

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  1. Yan Yu
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  2. Willis Li
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  3. Kai Su
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  4. Miyuki Yussa
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  5. Wei Han
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  6. Norbert Perrimon
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  7. Leslie Pick
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Yu, Y., Li, W., Su, K. et al. The nuclear hormone receptor Ftz-F1 is a cofactor for the Drosophila homeodomain protein Ftz. Nature 385, 552–555 (1997). https://doi.org/10.1038/385552a0

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