Pygopus, a nuclear PHD-finger protein required for Wingless signaling in Drosophila.

The secreted glycoprotein Wingless (Wg) acts through a conserved signaling pathway to regulate target gene expression. Wg signaling causes nuclear translocation of Armadillo, the fly beta-catenin, which then complexes with the DNA-binding protein TCF, enabling it to activate transcription. Though many nuclear factors have been implicated in modulating TCF/Armadillo activity, their importance remains poorly understood. This work describes a ubiquitously expressed protein, called Pygopus, which is required for Wg signaling throughout Drosophila development. Pygopus contains a PHD finger at its C terminus, a motif often found in chromatin remodeling factors. Overexpression of pygopus also blocks the pathway, consistent with the protein acting in a complex. The pygopus mutant phenotype is highly, though not exclusively, specific for Wg signaling. Epistasis experiments indicate that Pygopus acts downstream of Armadillo nuclear import, consistent with the nuclear location of heterologously expressed protein. Our data argue strongly that Pygopus is a new core component of the Wg signaling pathway that acts downstream or at the level of TCF.