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Dicer and Hsp104 function in a negative feedback loop to confer epigenetic robustness

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Schizosaccharomyces pombe

PROVIDER: GSE60640 | GEO | 2015/04/23

SECONDARY ACCESSION(S): PRJNA259168

REPOSITORIES: GEO

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Dicer and Hsp104 function in a negative feedback loop to confer epigenetic robustness

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2015-04-23 | E-GEOD-60640 | biostudies-arrayexpress

Dicer and Hsp104 function in a negative feedback loop to confer epigenetic robustness [RNA_correlations]

Project description:Epigenetic mechanisms can be influenced by environmental cues and thus evoke phenotypic variation. This plasticity can be advantageous for adaption, but also detrimental if not under tight control. Although having attracted considerable interest, it remains largely unknown if and how environmental cues such as temperature trigger epigenetic alterations. Using fission yeast, we demonstrate that environmentally induced discontinuous phenotypic variation is buffered by a negative feedback loop that involves the RNase Dicer and the protein disaggregase Hsp104. In the absence of Hsp104, Dicer accumulates in cytoplasmic inclusions and heterochromatin becomes unstable at elevated temperatures, an epigenetic state that is inherited for many generations after the heat stress. Dicer instead averts the toxic aggregation of a prionogenic protein. Our results highlight the importance of feedback regulation in building epigenetic memory and uncover Hsp104 and Dicer as homeostatic controllers that buffer environmentally induced stochastic epigenetic variation and toxic aggregation of prionogenic proteins. Various strains grown at 30°C or 37°C

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Negative feedback enhances robustness in the yeast polarity establishment circuit.

Project description:Many cells undergo symmetry-breaking polarization toward a randomly oriented "front" in the absence of spatial cues. In budding yeast, such polarization involves a positive feedback loop that enables amplification of stochastically arising clusters of polarity factors. Previous mathematical modeling suggested that, if more than one cluster were amplified, the clusters would compete for limiting resources and the largest would "win," explaining why yeast cells always make one and only one bud. Here, using imaging with improved spatiotemporal resolution, we show the transient coexistence of multiple clusters during polarity establishment, as predicted by the model. Unexpectedly, we also find that initial polarity factor clustering is oscillatory, revealing the presence of a negative feedback loop that disperses the factors. Mathematical modeling predicts that negative feedback would confer robustness to the polarity circuit and make the kinetics of competition between polarity factor clusters relatively insensitive to polarity factor concentration. These predictions are confirmed experimentally.

| S-EPMC3680131 | biostudies-literature

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