Selection of distinct Hox-Extradenticle interaction modes fine-tunes Hox protein activity.
Hox genes encode transcription factors widely used for diversifying animal body plans in development and evolution. To achieve functional specificity, Hox proteins associate with PBC class proteins, Pre-B cell leukemia homeobox (Pbx) in vertebrates, and Extradenticle (Exd) in Drosophila, and were thought to use a unique hexapeptide-dependent generic mode of interaction. Recent findings, however, revealed the existence of an alternative, UbdA-dependent paralog-specific interaction mode providing diversity in Hox-PBC interactions. In this study, we investigated the basis for the selection of one of these two Hox-PBC interaction modes. Using naturally occurring variations and mutations in the Drosophila Ultrabithorax protein, we found that the linker region, a short domain separating the hexapeptide from the homeodomain, promotes an interaction mediated by the UbdA domain in a context-dependent manner. While using a UbdA-dependent interaction for the repression of the limb-promoting gene Distalless, interaction with Exd during segment-identity specification still relies on the hexapeptide motif. We further show that distinctly assembled Hox-PBC complexes display subtle but distinct repressive activities. These findings identify Hox-PBC interaction as a template for subtle regulation of Hox protein activity that may have played a major role in the diversification of Hox protein function in development and evolution.
Institut de Biologie du Développement de Marseille Luminy, Centre National de la Recherche Scientifique, Université de la Méditerranée, 13288 Marseille Cedex 09, France.
Mehdi
M
Saadaoui
Samir
S
Merabet
Isma
I
Litim-Mecheri
Elise
E
Arbeille
Nagraj
N
Sambrani
Wim
W
Damen
Carlo
C
Brena
Jacques
J
Pradel
Yacine
Y
Graba
D020816:Amino Acid Motifs; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D019143:Evolution, Molecular; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C066177:Ubx protein, Drosophila; C083405:exd protein, Drosophila
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