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MBD5 and MBD6 interact with the human PR-DUB complex through their methyl-CpG-binding domain

Authors

  • H. Irem Baymaz,

    1. Molecular Cancer Research, Cancer Genomics, University Medical Center Utrecht, Utrecht, The Netherlands
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    • These authors have contributed equally to this work.

  • Alexandra Fournier,

    1. Epigenetics and Cell Fate, Sorbonne Paris Cité, Université Paris Diderot, Paris, France
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    • These authors have contributed equally to this work.

  • Sophie Laget,

    1. Epigenetics and Cell Fate, Sorbonne Paris Cité, Université Paris Diderot, Paris, France
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  • Zongling Ji,

    1. Faculty of Life Sciences, University of Manchester, Manchester, UK
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  • Pascal W. T. C. Jansen,

    1. Molecular Cancer Research, Cancer Genomics, University Medical Center Utrecht, Utrecht, The Netherlands
    Current affiliation:
    1. Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, The Netherlands
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  • Arne H. Smits,

    1. Molecular Cancer Research, Cancer Genomics, University Medical Center Utrecht, Utrecht, The Netherlands
    Current affiliation:
    1. Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, The Netherlands
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  • Laure Ferry,

    1. Epigenetics and Cell Fate, Sorbonne Paris Cité, Université Paris Diderot, Paris, France
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  • Anneloes Mensinga,

    1. Molecular Cancer Research, Cancer Genomics, University Medical Center Utrecht, Utrecht, The Netherlands
    Current affiliation:
    1. Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, The Netherlands
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  • Ina Poser,

    1. Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
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  • Andrew Sharrocks,

    1. Faculty of Life Sciences, University of Manchester, Manchester, UK
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  • Pierre-Antoine Defossez,

    Corresponding author
    1. Epigenetics and Cell Fate, Sorbonne Paris Cité, Université Paris Diderot, Paris, France
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  • Michiel Vermeulen

    1. Molecular Cancer Research, Cancer Genomics, University Medical Center Utrecht, Utrecht, The Netherlands
    Current affiliation:
    1. Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, The Netherlands
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Abstract

MBD5 and MBD6 are two members of the methyl-CpG-binding domain (MBD) family of proteins that are poorly characterized. Studies performed thus far have failed to show binding of the MBD5 and MBD6 MBD to methylated DNA. Here, we show that both MBD5 and MBD6 interact with the mammalian PR-DUB Polycomb protein complex in a mutually exclusive manner. Strikingly, the MBD of MBD5 and MBD6 is both necessary and sufficient to mediate this interaction. Chromatin immunoprecipitation analyses reveal that MBD6 and FOXK2/PR-DUB share a subset of genomic target genes, suggesting a functional interaction in vivo. Finally, we show that MBD6, but not MBD5, is recruited to sites of DNA damage in a PR-DUB independent manner. Our study thus implies a shared function for MBD5 and MBD6 through an interaction with PR-DUB, as well as an MBD6-specific recruitment to sites of DNA damage.

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