title: Variable motif utilization in homeotic selector (Hox)-cofactor complex formation controls specificity.
abstract: Homeotic selector (Hox) proteins often bind DNA cooperatively with cofactors such as Extradenticle (Exd) and Homothorax (Hth) to achieve functional specificity in vivo. Previous studies identified the Hox YPWM motif as an important Exd interaction motif. Using a comparative approach, we characterize the contribution of this and additional conserved sequence motifs to the regulation of specific target genes for three Drosophila Hox proteins. We find that Sex combs reduced (Scr) uses a simple interaction mechanism, where a single tryptophan-containing motif is necessary for Exd-dependent DNA-binding and in vivo functions. Abdominal-A (AbdA) is more complex, using multiple conserved motifs in a context-dependent manner. Lastly, Ultrabithorax (Ubx) is the most flexible, in that it uses multiple conserved motifs that function in parallel to regulate target genes in vivo. We propose that using different binding mechanisms with the same cofactor may be one strategy to achieve functional specificity in vivo.
authors.affiliation: Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Lelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Noro
authors.forename: Richard S
authors.initials: RS
authors.lastname: Mann
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics* / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence / Q000235:genetics; D004247:DNA / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004926:Escherichia coli; D005786:Gene Expression Regulation / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C410542:Abd-A protein, insect; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D046912:Multiprotein Complexes; C059627:Scr protein, Drosophila; D014157:Transcription Factors; C066177:Ubx protein, Drosophila; C083405:exd protein, Drosophila; D004247:DNA