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Mapping functional specificity in the Dfd and Ubx homeo domains.
1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06511.
Genes & Development
|June 1, 1992
Summary
Specific amino acids in the Ultrabithorax homeodomain control embryonic targeting. These residues, when part of a Deformed protein, switch its specificity to Ultrabithorax-like, impacting gene regulation.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Homeotic proteins are crucial for embryonic development, determining segment identity.
- Understanding the specificity of homeotic protein targeting is key to deciphering developmental pathways.
Purpose of the Study:
- To identify specific subregions within the homeodomain of homeotic proteins that dictate embryonic targeting specificity.
- To investigate how alterations in the Deformed (Dfd) homeodomain affect its interaction with target genes.
Main Methods:
- Construction of Deformed/Ultrabithorax chimeric genes by swapping homeobox regions.
- Introduction of chimeric genes into Drosophila melanogaster via P-element transformation.
- Analysis of cuticular phenotypes and transcriptional regulation following ectopic expression.
Main Results:
- Specific amino acid residues at the amino terminus of the Ultrabithorax (Ubx) homeodomain are essential for regulating Antennapedia (Antp) transcription.
- In a Deformed protein context, these Ubx amino-terminal residues are sufficient to confer Ubx-like targeting specificity.
- While the amino terminus of the Dfd homeodomain is important for Dfd-like specificity, other Dfd homeodomain regions are also necessary for full activity.
Conclusions:
- The amino terminus of the homeodomain plays a critical role in determining the targeting specificity of homeotic proteins.
- Chimeric protein analysis reveals a modularity in homeodomain function, allowing for switches in target gene recognition.