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Meneghini, M. D.

Publications and source records attributed to Meneghini, M. D..

2 recordsLinked to original sources

Nutritional and meiotic induction of heritable stress resistance states in budding yeast

Transient exposures to environmental stresses induce altered physiological states in exposed cells that persist after the stresses have been removed. These states, referred to as cellular memory, can even be passed on to daughter cells and may thus be thought of as embodying a form of epigenetic inheritance. We find that meiotically produced spores in the budding yeast S. cerevisiae possess a state of heightened stress resistance that, following their germination, persists for numerous mitotic generations. As yeast meiotic development is essentially a starvation response that a/alpha diploid cells engage, we sought to model this phenomenon by subjecting haploid cells to starvation conditions. We find also that haploid cells exposed to glucose withdrawal acquire a state of elevated stress resistance that persists after the reintroduction of these cells to glucose-replete media. Following release from lengthy durations of glucose starvation, we confirm that this physiological state of enhanced stress resistance is propagated in descendants of the exposed cells through two mitotic divisions before fading from the population. In both haploid starved cells and diploid produced meiotic spores we show that their cellular memories are not attributable to trehalose, a widely regarded stress protectant that accumulates in these cell types. Moreover, the heritable stress resistant state induced by glucose starvation in haploid cells is independent of the Msn2/4 transcription factors, which are known to program cellular memory induced by exposure of cells to NaCl. Our findings identify new developmentally and nutritionally induced states of cellular memory that exhibit striking degrees of perdurance and mitotic heritability.

cell biology

Combinatorial Genetic Control of Rpd3S through histone H3K4 and H3K36 Methylation in Budding Yeast

Much of euchromatin regulation occurs through reversible methylation of histone H3 lysine-4 and lysine-36 (H3K4me and H3K36me). Using the budding yeast Saccharomyces cerevisiae, we previously found that levels of H3K4me modulated temperature sensitive alleles of the transcriptional elongation complex Spt6-Spn1 through an unknown H3K4me effector pathway. Here we identify the Rpd3S histone deacetylase complex as the H3K4me effector underlying these Spt6-Spn1 genetic interactions. Exploiting these Spt6-Spn1 genetic interactions, we show that H3K4me and H3K36me collaboratively impact Rpd3S function in an opposing manner. H3K36me is deposited by the histone methyltransferase Set2 and is known to promote Rpd3S function at RNA PolII transcribed open reading frames. Using genetic epistasis experiments, we find that mutations perturbing the Set2-H3K36me-Rpd3S pathway suppress the growth defects caused by temperature sensitive alleles of SPT6 and SPN1, illuminating that this pathway antagonizes Spt6-Spn1. Using these sensitive genetic assays, we also identify a role for H3K4me in antagonizing Rpd3S that functions through the Rpd3S subunit Rco1, which is known to bind H3 N-terminal tails in a manner that is prevented by H3K4me. Further genetic experiments reveal that the H3K4 and H3K36 demethylases JHD2 and RPH1 mediate this combinatorial control of Rpd3S. Finally, our studies also show that the Rpd3L complex, which acts at promoter-proximal regions of PolII transcribed genes, counters Rpd3S for genetic modulation of Spt6-Spn1, and that these two Rpd3 complexes balance the activities of each other. Our findings present the first evidence that H3K4me and H3K36me act combinatorially to control Rpd3S.

genetics