TY - JOUR TI - Aneuploidy as a cause of impaired chromatin silencing and mating-type specification in budding yeast AU - Mulla, Wahid A AU - Seidel, Chris W AU - Zhu, Jin AU - Tsai, Hung-Ji AU - Smith, Sarah E AU - Singh, Pushpendra AU - Bradford, William D AU - McCroskey, Scott AU - Nelliat, Anjali R AU - Conkright, Juliana AU - Peak, Allison AU - Malanowski, Kathryn E AU - Perera, Anoja G AU - Li, Rong A2 - Berman, Judith VL - 6 PY - 2017 DA - 2017/08/25 SP - e27991 C1 - eLife 2017;6:e27991 DO - 10.7554/eLife.27991 UR - https://doi.org/10.7554/eLife.27991 AB - 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. KW - aneuploidy KW - epigenetic instability KW - chromatin silencing KW - cellular differentiation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -