Haecker, Achim Qi, Dai Lilja, Tobias Moussian, Bernard Paulo Andrioli, Luiz Luschnig, Stefan Mannervik, Mattias <em>Drosophila</em> Brakeless Interacts with Atrophin and Is Required for Tailless-Mediated Transcriptional Repression in Early Embryos <div><p>Complex gene expression patterns in animal development are generated by the interplay of transcriptional activators and repressors at <em>cis</em>-regulatory DNA modules (CRMs). How repressors work is not well understood, but often involves interactions with co-repressors. We isolated mutations in the <em>brakeless</em> gene in a screen for maternal factors affecting segmentation of the <em>Drosophila</em> embryo. Brakeless, also known as Scribbler, or Master of thickveins, is a nuclear protein of unknown function. In <em>brakeless</em> embryos, we noted an expanded expression pattern of the <em>Krüppel (Kr)</em> and <em>knirps (kni)</em> genes. We found that Tailless-mediated repression of <em>kni</em> expression is impaired in <em>brakeless</em> mutants. Tailless and Brakeless bind each other in vitro and interact genetically. Brakeless is recruited to the <em>Kr</em> and <em>kni</em> CRMs, and represses transcription when tethered to DNA. This suggests that Brakeless is a novel co-repressor. Orphan nuclear receptors of the Tailless type also interact with Atrophin co-repressors. We show that both <em>Drosophila</em> and human Brakeless and Atrophin interact in vitro, and propose that they act together as a co-repressor complex in many developmental contexts. We discuss the possibility that human Brakeless homologs may influence the toxicity of polyglutamine-expanded Atrophin-1, which causes the human neurodegenerative disease dentatorubral-pallidoluysian atrophy (DRPLA).</p> </div> brakeless;interacts;atrophin;tailless-mediated;transcriptional;repression;embryos 2007-05-15
    https://plos.figshare.com/articles/dataset/_Drosophila_Brakeless_Interacts_with_Atrophin_and_Is_Required_for_Tailless_Mediated_Transcriptional_Repression_in_Early_Embryos_/152413
10.1371/journal.pbio.0050145