Bcl9 and Pygo synergize downstream of Apc to effect intestinal neoplasia in mouse models recapitulating Familial Adenomatous Polyposis (Illumina Beadchip)

Bcl9 and Pygo function within the Wnt enhanceosome to effect β-catenin-dependent transcription. Whether they also mediate β-catenin-dependent neoplasia is unclear. Here we assess their roles in intestinal tumorigenesis initiated by Apc loss-of-function (ApcMin). Gene expression profiling revealed that loss-of-Bcl9 synergizes with loss-of-Pygo to shift gene expression within Apc-mutant adenomas from stem cell-like to differentiation along Notch-regulated secretory lineages. Total RNA was isolated from EDTA-dissociated crypt epithelium or intestinal ApcMin adenomas of wild type (wt), Bcl9/B9l double knockout (DKO), Pygo 1/2 DKO, or Bcl9/B9l & Pygo 1/2 quadruple knockout (QKO) mice, and analysed for differential gene expression using Illumina MouseWG-6 v2.0 expression beadchips.