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

Wahid A. Mulla, Chris W. Seidel, Jin Zhu, Hung Ji Tsai, Sarah E. Smith, Pushpendra Singh, William D. Bradford, Scott McCroskey, Anjali R. Nelliat, Juliana Conkright, Allison Peak, Kathryn E. Malanowski, Anoja G. Perera, Rong Li

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere27991
JournaleLife
Volume6
DOIs
StatePublished - Aug 25 2017

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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