Aneuploidy as a cause of impaired chromatin silencing and mating-type specification in budding yeast
- Johns Hopkins University, United States
- Stowers Institute for Medical Research, United States
- Johns Hopkins, United States
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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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.
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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Aneuploidy as a cause of impaired chromatin silencing and mating-type specification in budding yeast
eLife 6:e27991.
https://doi.org/10.7554/eLife.27991
