ChIP-chip from mouse keratinocytes with Plakoglobin and β-catenin. Mus musculus

Plakoglobin (PG; γ-Catenin, JUP) is a protein with controversial function. First described as a component of intercellular junctions, it has remained unresolved whether this near-ubiquitously expressed protein acts as a genuine transcriptional regulator in adult tissue like its closest relative β-catenin. Here we have mapped the global gene targets of PG by ChIP-chip in differentiating skin keratinocytes. Applying a peak algorithm, over 5’000 high-confidence PG target promoters were identified and 2’000 for β-catenin with an overlap of 38%. Bioinformatics analyses most significantly associated PG target genes with the Wnt signaling pathway as well as relevant pathways for keratinocyte differentiation. Using a combination of wild-type, PG, β-catenin and PG/β-catenin double null keratinocytes, PG was functionally validated as a LEF/TCF-dependent transcriptional regulator. These data challenge the current understanding of Wnt signaling, one of the most important pathways in tissue homeostasis, by identifying PG as a potent LEF/TCF-dependent transcriptional regulator which functionally overlaps with β-catenin. Overall design: comparison of Plakoglobin and β-catenin binding to promoters in mouse keratinocytes at the onset of terminal differentiation