1. Cell Biology
  2. Chromosomes and Gene Expression
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Aneuploidy as a cause of impaired chromatin silencing and mating-type specification in budding yeast

  1. Wahid A Mulla
  2. Chris W Seidel
  3. Jin Zhu
  4. Hung-Ji Tsai
  5. Sarah E Smith
  6. Pushpendra Singh
  7. William D Bradford
  8. Scott McCroskey
  9. Anjali R Nelliat
  10. Juliana Conkright
  11. Allison Peak
  12. Kathryn E Malanowski
  13. Anoja G Perera
  14. Rong Li  Is a corresponding author
  1. Johns Hopkins University, United States
  2. Stowers Institute for Medical Research, United States
  3. Johns Hopkins, United States
Research Article
  • Cited 14
  • Views 2,487
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Cite this article as: eLife 2017;6:e27991 doi: 10.7554/eLife.27991

Abstract

Aneuploidy and epigenetic alterations have long been associated with carcinogenesis, but it was unknown whether aneuploidy could disrupt the epigenetic states required for cellular differentiation. In this study, we found that ~3% of random aneuploid karyotypes in yeast disrupt the stable inheritance of silenced chromatin during cell proliferation. Karyotype analysis revealed that this phenotype was significantly correlated with gains of chromosomes III and X. Chromosome X disomy alone was sufficient to disrupt chromatin silencing and yeast mating-type identity as indicated by a lack of growth response to pheromone. The silencing defect was not limited to cryptic mating type loci and was associated with broad changes in histone modifications and chromatin localization of Sir2 histone deacetylase. The chromatin-silencing defect of disome X can be partially recapitulated by an extra copy of several genes on chromosome X. These results suggest that aneuploidy can directly cause epigenetic instability and disrupt cellular differentiation.

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Author details

  1. Wahid A Mulla

    Department of Cell Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3356-3902
  2. Chris W Seidel

    Genomics, Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jin Zhu

    Department of Cell Biology, Johns Hopkins, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Hung-Ji Tsai

    Cell Biology, Johns Hopkins, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sarah E Smith

    Imaging Facility, Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Pushpendra Singh

    Cell Biology, Johns Hopkins, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. William D Bradford

    Molecular Biology, Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Scott McCroskey

    Molecular Biology, Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Anjali R Nelliat

    Chemical and Biomolecular Engineering, Johns Hopkins, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Juliana Conkright

    Screening core, Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Allison Peak

    Molecular Biology Core, Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Kathryn E Malanowski

    Molecular Biology Core, Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Anoja G Perera

    Molecular Biology, Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Rong Li

    Cell Biology, Johns Hopkins, Baltimore, United States
    For correspondence
    rong@jhu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0540-6566

Funding

National Institute of General Medical Sciences (R35-GM118172)

  • Rong Li

American Heart Association (15PRE25090204)

  • Wahid A Mulla

Prostate Cancer Foundation (16YOUN21)

  • Hung-Ji Tsai

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Judith Berman, Tel Aviv University, Israel

Publication history

  1. Received: April 21, 2017
  2. Accepted: August 24, 2017
  3. Accepted Manuscript published: August 25, 2017 (version 1)
  4. Version of Record published: September 22, 2017 (version 2)

Copyright

© 2017, Mulla 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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