A role of Pygopus as an anti-repressor in facilitating Wnt-dependent transcription

Wnt/β-catenin signaling controls animal development and tissue homeostasis, and is also an important cancer pathway. Pygopus (Pygo) is a conserved nuclear Wnt signaling component that is essential for Wingless-induced transcription throughoutDrosophila development. It associates with Armadillo/β-catenin and T cell factor (TCF) through the Legless/BCL9 adaptor, but its molecular function in TCF-mediated transcription is unknown. Here, we use agroucho -null allele to show that Groucho represses Wingless target genes duringDrosophila development. Interestingly,groucho pygo double-mutants revealed that Pygo is not obligatory for transcriptional and phenotypic Wingless signaling outputs if the interaction between Groucho andDrosophila TCF is compromised genetically. Pygo function is also non-essential for Wingless outputs in the absence of other transcriptional antagonists of Wingless signaling. This indicates an anti-repressor function of Pygo: we propose that Pygo predisposesDrosophila TCF target genes for rapid Wingless-induced transcription, or that it protects them against premature shut-down.