1. Structural Biology and Molecular Biophysics
  2. Chromosomes and Gene Expression
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PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3

  1. Ho-Ryun Chung
  2. Chao Xu
  3. Alisa Fuchs
  4. Andreas Mund
  5. Martin Lange
  6. Hannah Staege
  7. Tobias Schubert
  8. Chuanbing Bian
  9. Ilona Dunkel
  10. Anton Eberharter
  11. Catherine Regnard
  12. Henrike Klinker
  13. David Meierhofer
  14. Luca Cozzuto
  15. Andreas Winterpacht
  16. Luciano Di Croce
  17. Jinrong Min
  18. Hans Will
  19. Sarah Kinkley  Is a corresponding author
  1. Max Planck Institute for Molecular Genetics, Germany
  2. Structural Genomics Consortium, Canada
  3. Heinrich-Pette-Institute - Leibniz Institute for Experimental Virology, Germany
  4. Bayer Pharma AG, Germany
  5. Ludwig-Maximilians-University, Germany
  6. Centre for Genomic Regulation, Spain
  7. Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany
Research Article
  • Cited 13
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Cite this article as: eLife 2016;5:e10607 doi: 10.7554/eLife.10607

Abstract

PHF13 is a chromatin affiliated protein with a functional role in differentiation, cell division, DNA damage response and higher chromatin order. To gain insight into PHF13's ability to modulate these processes, we elucidate the mechanisms targeting PHF13 to chromatin, its genome wide localization and its molecular chromatin context. Size exclusion chromatography, mass spectrometry, X-ray crystallography and ChIP sequencing demonstrate that PHF13 binds chromatin in a multivalent fashion via direct interactions with H3K4me2/3 and DNA, and indirectly via interactions with PRC2 and RNA PolII. Furthermore, PHF13 depletion disrupted the interactions between PRC2, RNA PolII S5P, H3K4me3 and H3K27me3 and resulted in the up and down regulation of genes functionally enriched in transcriptional regulation, DNA binding, cell cycle, differentiation and chromatin organization. Together our findings argue that PHF13 is an H3K4me2/3 molecular reader and transcriptional co-regulator, affording it the ability to impact different chromatin processes.

Article and author information

Author details

  1. Ho-Ryun Chung

    Max Planck Institute for Molecular Genetics, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Chao Xu

    Structural Genomics Consortium, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Alisa Fuchs

    Max Planck Institute for Molecular Genetics, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Andreas Mund

    Heinrich-Pette-Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Martin Lange

    TRG-ONCI, Bayer Pharma AG, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Hannah Staege

    Heinrich-Pette-Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Tobias Schubert

    Heinrich-Pette-Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Chuanbing Bian

    Structural Genomics Consortium, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  9. Ilona Dunkel

    Max Planck Institute for Molecular Genetics, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Anton Eberharter

    Adolf-Butenandt-Institute and Center for Integrated Protein Science, Ludwig-Maximilians-University, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Catherine Regnard

    Adolf-Butenandt-Institute and Center for Integrated Protein Science, Ludwig-Maximilians-University, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  12. Henrike Klinker

    Adolf-Butenandt-Institute and Center for Integrated Protein Science, Ludwig-Maximilians-University, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  13. David Meierhofer

    Max Planck Institute for Molecular Genetics, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  14. Luca Cozzuto

    Centre for Genomic Regulation, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  15. Andreas Winterpacht

    Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  16. Luciano Di Croce

    Centre for Genomic Regulation, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  17. Jinrong Min

    Structural Genomics Consortium, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  18. Hans Will

    Heinrich-Pette-Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  19. Sarah Kinkley

    Max Planck Institute for Molecular Genetics, Berlin, Germany
    For correspondence
    kinkley@molgen.mpg.de
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Jessica K Tyler, Weill Cornell Medicine, United States

Publication history

  1. Received: August 4, 2015
  2. Accepted: May 19, 2016
  3. Accepted Manuscript published: May 25, 2016 (version 1)
  4. Accepted Manuscript updated: May 26, 2016 (version 2)
  5. Accepted Manuscript updated: May 27, 2016 (version 3)
  6. Version of Record published: June 21, 2016 (version 4)

Copyright

© 2016, Ho-Ryun 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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