Origins of Context-Dependent Gene Repression by Capicua

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Understanding the evolution of developmental regulatory mechanisms is a central challenge of biology. Here we uncover a newly evolved mechanism of transcriptional repression by Capicua (Cic), a conserved sensor of Receptor Tyrosine Kinase (RTK) signaling. In Drosophila, Cic patterns the central regions of the embryo by repressing genes induced by Torso RTK signaling at the poles. We show that Cic performs this function by recruiting the Groucho (Gro) corepressor and that this mechanism is an evolutionary innovation of dipteran insects. Indeed, we find that recruitment of Gro depends on a short motif of Cic (N2) specific to dipterans. Strikingly, moreover, the form of Cic that existed before the origin of dipterans is completely inactive in fly embryos, whereas the equivalent form carrying N2 displays significant function. This suggests that evolution of the N2 motif caused a fundamental change in Cic repressor activity, which we propose has enabled the complex roles of Cic, Gro and Torso signaling in fly embryonic patterning. In contrast, Cic functions independently of Gro in other Drosophila tissues and probably also in mammals, where Cic lacks the N2 sequence. Thus, our results illustrate the structural and evolutionary origins of essential functional variations within a highly conserved family of developmental regulators.

Vyšlo v časopise: Origins of Context-Dependent Gene Repression by Capicua. PLoS Genet 11(1): e32767. doi:10.1371/journal.pgen.1004902
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004902

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