Abstract
AbstractPhenotypic diversity and fidelity can be balanced by controlling stochastic molecular mechanisms. Epigenetic silencing is one that has a critical role in stress response. Here we show that in yeast, incomplete silencing increases stochastic noise in gene expression, probably owing to unstable chromatin structure. Telomere position effect is suggested as one mechanism. Expression diversity in a population achieved in this way may render a subset of cells to readily respond to various acute stresses. By contrast, strong silencing tends to suppress noisy expression of genes, in particular those involved in life cycle control. In this regime, chromatin may act as a noise filter for precisely regulated responses to environmental signals that induce huge phenotypic changes such as a cell fate transition. These results propose modulation of chromatin stability as an important determinant of environmental adaptation and cellular differentiation.
Highlights
Phenotypic switching can be dictated by epigenetic switching of gene expression
The model suggests that the relevant genes are located in regions of silent chromatin; reduced silencing activity resulting from Sir[2] disruption increases switching frequencies of their expression by destabilizing silent chromatin, mimicking telomere position effect in S. cerevisiae 8
The frequency of switching will eventually be reflected in gene expression noise, which is measured on a genomic scale by a recent study 14
Summary
Estimation and evaluation of Sir2/3/4- and Set1-mediated silencing activity. Expression change of each yeast gene accompanying the deletion of Sir2/3/4 and Set[1] was measured[31,32]. We observed that for both Sir2/3/4 and Set[1], genes with 0.5 < silencing activity < 1.0 showed highest levels of expression noise (Fig. 2A). Functional implications of silencing activity in terms of Gene Ontology categories. Using the Gene Ontology hierarchy, we mapped each gene to all its parent categories. We calculated the average silencing activity of Sir2/3/4 and Set[1] for genes in each category. Silencing activity and expression noise for stress-responsive gene sets or Gene Ontology categories. See Supplementary Information online for defining gene sets. (P value) indicates that the genes in the set have higher silencing activity or expression noise compared with other genes. The Bonferroni correction was used to set the threshold to 0.001
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