1. Structural Biology and Molecular Biophysics
  2. Developmental Biology
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An ancient Pygo-dependent Wnt enhanceosome integrated by Chip/LDB-SSDP

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Cite this article as: eLife 2015;4:e09073 doi: 10.7554/eLife.09073

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.

Article and author information

Author details

  1. Marc Fiedler

    MRC Laboratory of Molecular Biology, Medical Research Council, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Michael Graeb

    MRC Laboratory of Molecular Biology, Medical Research Council, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Juliusz Mieszczanek

    MRC Laboratory of Molecular Biology, Medical Research Council, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Trevor J Rutherford

    MRC Laboratory of Molecular Biology, Medical Research Council, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Christopher M Johnson

    MRC Laboratory of Molecular Biology, Medical Research Council, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Mariann Bienz

    MRC Laboratory of Molecular Biology, Medical Research Council, Cambridge, United Kingdom
    For correspondence
    mb2@mrc-lmb.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Robb Krumlauf, Stowers Institute for Medical Research, United States

Publication history

  1. Received: May 29, 2015
  2. Accepted: August 26, 2015
  3. Accepted Manuscript published: August 27, 2015 (version 1)
  4. Version of Record published: September 16, 2015 (version 2)

Copyright

© 2015, Fiedler et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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