SRA

Stress can spur the redistribution of histone modifications to establish novel phenotypes. We do not understand how cells leverage existing epigenetic pathways to establish and maintain new gene expression states that enhance fitness and cell survival. H3K9 methylation promotes epigenetic silencing in fission yeast (S. pombe). Heterochromatin establishment depends on the H3K9 methyltransferase, Clr4 and is opposed by two major two heterochromatin regulators, Epe1, a putative H3K9 demethylase and Mst2, an H3K14 acetyltransferase. We designed an inducible system in mst2D cells to toggle Epe1 availability on-demand and trigger heterochromatin misregulation thus initiating an adaptive epigenetic response. Following Epe1 depletion, we mapped transcriptome and H3K9me3 changes as a function of time. Although Epe1 could be removed in ~30 minutes, the population of cells took two orders of magnitude longer to establish an adaptive phenotype. Similarly, re-expressing Epe1 did not switch cells back to their initial state. Instead, cells exhibit unique transcriptional signatures during recovery that encode adaptive memory that is both reversible and tunable. Our results reveal that the slow kinetics of chromatin state changes enable bet-hedging for cells to identify optimal adaptive solutions while hysteresis within the gene regulatory network encodes cellular memory. Overall design: Comparative gene expression profiling analysis of RNA-seq data, performed in triplicate, under several genotypic backgrounds. Epe1-deg strains contained a modified, suppressible epe1 gene locus. Epe1 was suppressed and samples were drawn at 24 hour time intervals. Recovery samples had Epe1 returned, following 120 hours of Epe1 depletion. Short recovery was 24 hours +Epe1, medium recovery was 48 hours +Epe1. Other strains were grown in neutral media.