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