Open Close
Reference
Citation
Fiedler, M., Graeb, M., Mieszczanek, J., Rutherford, T.J., Johnson, C.M., Bienz, M. (2015). An ancient Pygo-dependent Wnt enhanceosome integrated by Chip/LDB-SSDP.  eLife 4(): e09073.
FlyBase ID
FBrf0229654
Publication Type
Research paper
Abstract

TCF/LEF factors are ancient context-dependent enhancer-binding proteins that are activated by β-catenin following Wnt signaling. They control embryonic development and adult stem cell compartments, and their dysregulation often causes cancer. β-catenin-dependent transcription relies on the NPF motif of Pygo proteins. Here, we use a proteomics approach to discover the Chip/LDB-SSDP (ChiLS) complex as the ligand specifically binding to NPF. ChiLS also recognizes NPF motifs in other nuclear factors including Runt/RUNX2 and Drosophila ARID1, and binds to Groucho/TLE. Studies of Wnt-responsive dTCF enhancers in the Drosophila embryonic midgut indicate how these factors interact to form the Wnt enhanceosome, primed for Wnt responses by Pygo. Together with previous evidence, our study indicates that ChiLS confers context-dependence on TCF/LEF by integrating multiple inputs from lineage and signal-responsive factors, including enhanceosome switch-off by Notch. Its pivotal function in embryos and stem cells explain why its integrity is crucial in the avoidance of cancer.

PubMed ID
PubMed Central ID
PMC4571689 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    eLife
    Title
    eLife
    ISBN/ISSN
    2050-084X
    Data From Reference
    Alleles (12)
    Gene Groups (1)
    Genes (24)
    Physical Interactions (8)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (1)
    Transgenic Constructs (6)