GSE210305
A screen for histone mutations that affect quiescence in S. cerevisiae.
Quiescence is a distinct cell cycle phase, termed G0, in which growth, transcription, translation, and replication are suppressed. Yeast cells enter G0 following glucose exhaustion but remain viable for an extended period and can re-enter the cell cycle when returned to glucose-rich medium. Quiescence is a feature of all organisms and is essential for the maintenance of stem cells and tissue renewal. Quiescence is also related to chronological lifespan (CLS) - or the capacity of post-mitotic quiescent cells to survive over time - and thus contributes to longevity. However, important questions remain to be answered regarding the mechanisms that control entry into quiescence, the maintenance of quiescence, and the re-entry of quiescent cells into the cell cycle. Histone acetylation is lost during the formation of quiescent yeast cells, and chromatin becomes highly condensed. This unique chromatin landscape plays a key role in supporting quiescence-specific transcriptional repression and has been linked to the formation and maintenance of quiescent cells. To ask if other chromatin features regulate quiescence, we conducted a comprehensive screen of histone H3 and H4 mutants. We identified several mutants that show altered quiescence entry and have characterized their chromatin phenotypes. None of these mutants retain histone acetylation, while several have altered chromatin condensation. Additionally, a screen for H3 and H4 mutants with altered chronological lifespan showed that CLS is highly correlated with quiescence entry. Overall design: The H3/H4 mutant library was pooled for co-culturing. Proliferating (Log), isolated quiescent, stationary phase, and released stationary phase cells were collected from the pooled culture, gDNA isolate, and subjected to Bar-seq analysis to quantify the number of mutants in the pooled population.