@article{eb9b3efc42da4cbc958c2ada4b79a11b,
title = "Aneuploidy as a cause of impaired chromatin silencing and mating-type specification in budding yeast",
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.",
author = "Mulla, {Wahid A.} and Seidel, {Chris W.} and Jin Zhu and Tsai, {Hung Ji} and Smith, {Sarah E.} and Pushpendra Singh and Bradford, {William D.} and Scott McCroskey and Nelliat, {Anjali R.} and Juliana Conkright and Allison Peak and Malanowski, {Kathryn E.} and Perera, {Anoja G.} and Rong Li",
note = "Funding Information: We thank James Broach, James E Haber and Rodney Rothstein for providing yeast strains; Adam Rudner for providing Sir2 antibody; Guangbo Chen, Tamara Potapova, Andrei Kucharavy, and Swa-minathan Venkatesh, and Andy Feinberg for helpful advice; Kristen Swaney for critically reading the manuscript; Jay Unruh, Brian Slaughter, Sreekumar Ramachandran, Neil Neumann, and Dan Geor-gess for assistance on microscopy and image analysis; W McDowell and Brian Flaherty for help with qPCR; and Akshay Narkar for help with western blotting. This work was supported by NIH grant R35-GM118172 to RL, American Heart Association predoctoral fellowship 15PRE25090204 to WM, and Prostate Cancer Foundation Young Investigator Award 16YOUN21 to HJT. The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.",
year = "2017",
month = aug,
day = "25",
doi = "10.7554/eLife.27991",
language = "English (US)",
volume = "6",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}