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Selection of distinct Hox-Extradenticle interaction modes fine-tunes Hox protein activity.

Abstract : 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.
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Submitted on : Monday, July 29, 2013 - 2:43:50 PM
Last modification on : Tuesday, May 31, 2022 - 10:20:14 AM

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Mehdi Saadaoui, Samir Merabet, Isma Litim-Mecheri, Elise Arbeille, Nagraj Sambrani, et al.. Selection of distinct Hox-Extradenticle interaction modes fine-tunes Hox protein activity.. Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2011, 108 (6), pp.2276-81. ⟨10.1073/pnas.1006964108⟩. ⟨hal-00848905⟩

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