Cellular Memory of Acquired Stress Resistance inSaccharomyces cerevisiae

Abstract

Cellular memory of past experiences has been observed in several organisms and across a variety of experiences, including bacteria "remembering" prior nutritional status and amoeba "learning" to anticipate future environmental conditions. Here, we show that Saccharomyces cerevisiae maintains a multifaceted memory of prior stress exposure. We previously demonstrated that yeast cells exposed to a mild dose of salt acquire subsequent tolerance to severe doses of H 2 O 2 . We set out to characterize the retention of acquired tolerance and in the process uncovered two distinct aspects of cellular memory. First, we found that H 2 O 2 resistance persisted for four to five generations after cells were removed from the prior salt treatment and was transmitted to daughter cells that never directly experienced the pretreatment. Maintenance of this memory did not require nascent protein synthesis after the initial salt pretreatment, but rather required long-lived cytosolic catalase Ctt1p that was synthesized during salt exposure and then distributed to daughter cells during subsequent cell divisions. In addition to and separable from the memory of H 2 O 2 resistance, these cells also displayed a faster gene-expression response to subsequent stress at .1000 genes, representing transcriptional memory. The faster gene-expression response requires the nuclear pore component Nup42p and serves an important function by facilitating faster reacquisition of H 2 O 2 tolerance after a second cycle of salt exposure. Memory of prior stress exposure likely provides a significant advantage to microbial populations living in ever-changing environments. N ATURAL environments are complex and often vary significantly in space and time, posing challenges for the organisms living within them. Single-cell organisms are particularly vulnerable, since variation in external conditions can directly impact internal homeostasis. Therefore, preparing for environmental change after early signs of fluctuation would present a significant advantage for cells growing in the wild. Indeed, many organisms can become tolerant to severe stress after an initial mild pretreatment with the same or a different stressor. This response, termed "acquired stress resistance," has been observed in microbes such as bacteria and yeast as well as in multicellular organisms including worms, plants, mammals, and even humans (Lu et al. 1993;Davies et al. 1995;Lewis et al. 1995;Lou and Yousef 1997;Swan and Watson 1999;Chi and Arneborg 2000;Schenk et al. 2000;Durrant and Dong 2004;Kandror et al. 2004;Scholz et al. 2005;Hecker et al. 2007;Kensler et al. 2007;Matsumoto et al. 2007). The conservation of this response suggests that it plays an important role in surviving environmental stress in diverse species.We previously conducted a systematic analysis of acquired stress resistance in Saccharomyces cerevisiae and found that the response is common, but not universal, for all pairs of stress treatments (Berry and Gasch 2008). The level and duration of mild-stress pretreatme...

Different Mechanisms Confer Gradual Control and Memory at Nutrient- and Stress-Regulated Genes in Yeast

“…Therefore, stress-induced genes might be modulated predominantly by the cellular defense capacity, which determines the time needed to maintain maximal gene expression. It is worth noting that a positive memory effect has been reported recently for the yeast response to oxidative stress when the cells were previously treated with a mild dose of salt (52). Future work might therefore reveal the importance of acquired resistance versus transcriptional memory for different stress types and doses.…”

Nuclear pore proteins regulate chromatin structure and transcriptional memory by a conserved mechanism

“…Consistent with this notion, the promoters of stress-responsive yeast genes that exhibit a form of epigenetic transcriptional memory are enriched for an element that is very similar to the MRS element. 19 Also, these genes require Nup42 for this behavior. 19 If these genes are regulated by a mechanism similar to that used by INO1 and HLA-DRA, their promoters may be marked with H3K4me2 and bound to RNAPII following the primary stress.…”

“…19 Also, these genes require Nup42 for this behavior. 19 If these genes are regulated by a mechanism similar to that used by INO1 and HLA-DRA, their promoters may be marked with H3K4me2 and bound to RNAPII following the primary stress.…”

“…The promoters of stress-induced yeast genes that display transcriptional memory are enriched for a very similar element. 19 Furthermore, the MRS is sufficient to recapitulate the chromatin structure associated with transcriptional memory when inserted at ectopic loci. 1 However, the MRS is not sufficient to promote PIC association with an ectopic locus, suggesting that PIC association is a context-dependent (and presumably promoter-specific) output of transcriptional memory.…”

“…19 The mechanistic details for these genes are similar but not identical to INO1. 19 Furthermore, although there is a clear role for the interaction of Nups in promoting transcription in flies and humans, [20][21][22][23] it was unclear if metazoan Nups were also involved in transcriptional memory. A study published in 2010 suggested that the induction of the human HLA-DRA gene in response to interferon gamma (IFN-γ) was faster in cells that had previously been exposed to IFN-γ.…”