An H3K9 methylation dependent protein interaction regulates the non-enzymatic function of a putative histone demethylase

Abstract

H3K9 methylation (H3K9me) specifies the establishment and maintenance of transcriptionally silent epigenetic states or heterochromatin. The enzymatic erasure of histone modifications is widely assumed to be the primary mechanism that reverses epigenetic silencing. Here, we reveal an inversion of this paradigm where a putative histone demethylase Epe1 in fission yeast, has a non-enzymatic function that opposes heterochromatin assembly. Mutations within the putative catalytic JmjC domain of Epe1 disrupt its interaction with Swi6HP1 suggesting that it might have other functions besides enzymatic activity. The C-terminus of Epe1 directly interacts with Swi6HP1, and H3K9 methylation stimulates this protein-protein interaction in vitro and in vivo. Expressing the Epe1 C-terminus is sufficient to disrupt heterochromatin by outcompeting the histone deacetylase, Clr3 from sites of heterochromatin formation. Our results underscore how histone modifying proteins that resemble enzymes have non-catalytic functions that regulate the assembly of epigenetic complexes in cells.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Gulzhan Raiymbek

    Department of Biological Chemistry, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sojin An

    Department of Biological Chemistry, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Nidhi Khurana

    Department of Biological Chemistry, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Saarang Gopinath

    Department of Biological Chemistry, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ajay Larkin

    Department of Biological Chemistry, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Saikat Biswas

    Department of Biological Chemistry, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Raymond C Trievel

    Department of Biological Chemistry, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Uhn-soo Cho

    Department of Biological Chemistry, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6992-2455
  9. Kaushik Ragunathan

    Department of Biological Chemistry, University of Michigan, Ann Arbor, United States
    For correspondence
    ragunath@umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4776-8589

Funding

The authors declare that there was no external funding for this work.

Reviewing Editor

  1. Daniel Zilberman, John Innes Centre, United Kingdom

Publication history

  1. Received: October 30, 2019
  2. Accepted: March 19, 2020
  3. Accepted Manuscript published: March 20, 2020 (version 1)
  4. Version of Record published: April 30, 2020 (version 2)

Copyright

© 2020, Raiymbek 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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  1. Gulzhan Raiymbek
  2. Sojin An
  3. Nidhi Khurana
  4. Saarang Gopinath
  5. Ajay Larkin
  6. Saikat Biswas
  7. Raymond C Trievel
  8. Uhn-soo Cho
  9. Kaushik Ragunathan
(2020)
An H3K9 methylation dependent protein interaction regulates the non-enzymatic function of a putative histone demethylase
eLife 9:e53155.
https://doi.org/10.7554/eLife.53155

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