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Elife. 2017 Aug 25;6. pii: e27991. doi: 10.7554/eLife.27991.

Aneuploidy as a cause of impaired chromatin silencing and mating-type specification in budding yeast.

Author information

1
Department of Cell Biology, Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, United States.
2
Department of Medicine, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States.
3
Stowers Institute for Medical Research, Missouri, United States.
4
Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, 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.

KEYWORDS:

S. cerevisiae; aneuploidy; cell biology; cellular differentiation; chromatin silencing; chromosomes; epigenetic instability; genes

PMID:
28841138
PMCID:
PMC5779231
DOI:
10.7554/eLife.27991
[Indexed for MEDLINE]
Free PMC Article

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