title: Constitutive scaffolding of multiple Wnt enhanceosome components by Legless/BCL9.
abstract: Wnt/β-catenin signaling elicits context-dependent transcription switches that determine normal development and oncogenesis. These are mediated by the Wnt enhanceosome, a multiprotein complex binding to the Pygo chromatin reader and acting through TCF/LEF-responsive enhancers. Pygo renders this complex Wnt-responsive, by capturing β-catenin via the Legless/BCL9 adaptor. We used CRISPR/Cas9 genome engineering ofDrosophila legless (lgs)and humanBCL9andB9Lto show that the C-terminus downstream of their adaptor elements is crucial for Wnt responses. BioID proximity labeling revealed that BCL9 and B9L, like PYGO2, are constitutive components of the Wnt enhanceosome. Wnt-dependent docking of β-catenin to the enhanceosome apparently causes a rearrangement that apposes the BCL9/B9L C-terminus to TCF. This C-terminus binds to the Groucho/TLE co-repressor, and also to the Chip/LDB1-SSDP enhanceosome core complex via an evolutionary conserved element. An unexpected link between BCL9/B9L, PYGO2 and nuclear co-receptor complexes suggests that these β-catenin co-factors may coordinate Wnt and nuclear hormone responses.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Laurens M
authors.initials: LM
authors.lastname: van Tienen
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Juliusz
authors.initials: J
authors.lastname: Mieszczanek
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Marc
authors.initials: M
authors.lastname: Fiedler
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Rutherford
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Mariann
authors.identifier: 0000-0002-7170-8706
authors.initials: M
authors.lastname: Bienz
mesh_terms: D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D000072669:Gene Editing; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D014157:Transcription Factors; D060449:Wnt Signaling Pathway
chemical_list: C111180:BCL9 protein, human; D029721:Drosophila Proteins; C453403:Lgs protein, Drosophila; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D014157:Transcription Factors
keywords: BCL9/Legless; D. melanogaster; Groucho/TLE; Osa/ARID1A; Wnt enhanceosome complex; Wnt signalling pathway; biochemistry; cell biology; human; nuclear co-receptor complex