Dataset Information

Inheritance of a Phenotypically Neutral Epimutation Evokes Gene Silencing in Later Generations.

ABSTRACT: Small RNAs trigger the formation of epialleles that are silenced across generations. Consequently, RNA-directed epimutagenesis is associated with persistent gene repression. Here, we demonstrate that small interfering RNA-induced epimutations in fission yeast are still inherited even when the silenced gene is reactivated, and descendants can reinstate the silencing phenotype that only occurred in their ancestors. This process is mediated by the deposition of a phenotypically neutral molecular mark composed of tri-methylated histone H3 lysine 9 (H3K9me3). Its stable propagation is coupled to RNAi and requires maximal binding affinity of the Clr4/Suvar39 chromodomain to H3K9me3. In wild-type cells, this mark has no visible impact on transcription but causes gene silencing if RNA polymerase-associated factor 1 complex (Paf1C) activity is impaired. In sum, our results reveal a distinct form of epigenetic memory in which cells acquire heritable, transcriptionally active epialleles that confer gene silencing upon modulation of Paf1C.

SUBMITTER: Duempelmann L

PROVIDER: S-EPMC6509282 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Inheritance of a Phenotypically Neutral Epimutation Evokes Gene Silencing in Later Generations.

Duempelmann Lea L Mohn Fabio F Shimada Yukiko Y Oberti Daniele D Andriollo Aude A Lochs Silke S Bühler Marc M

Molecular cell 20190318 3

Small RNAs trigger the formation of epialleles that are silenced across generations. Consequently, RNA-directed epimutagenesis is associated with persistent gene repression. Here, we demonstrate that small interfering RNA-induced epimutations in fission yeast are still inherited even when the silenced gene is reactivated, and descendants can reinstate the silencing phenotype that only occurred in their ancestors. This process is mediated by the deposition of a phenotypically neutral molecular ma ...[more]

PMID: 30898439

Similar Datasets

Project description:Phenotypic differences caused by epimutations rather than changes in DNA sequence have been described in various organisms. Epimutations are potentially adaptive if inherited across generations and might even respond to environmental challenges. Yet experimental evidence is scarce1. Examples of heritable phenotypic changes are paramutation in plants and RNA-induced epigenetic silencing (RNAe) in nematodes, in which small RNAs trigger the formation of silent epialleles that are stable across generations2-7. Consequently, RNA-directed epimutagenesis has been associated with persistent gene repression. Here, using the fission yeast Schizosaccharomyces pombe, we demonstrate that RNA-induced epimutations are stably transmitted to subsequent generations also after reactivation of the silenced gene. This enables descendants to remember and reinstate preceding silencing episodes that had occurred in their ancestors. We show that temporary expression of hairpin-derived small interfering RNAs (siRNAs) triggers RNAe that is stably propagated for at least 18 generations upon inactivation of the polymerase-associated factor 1 complex (Paf1C). In the presence of Paf1C, the silent state is lost, but resumes if Paf1C is again impaired, even in the absence of the original trigger and in later generations. Thus, in yeast RNAe installs a molecular imprint that can be inherited through meiosis with no discernible phenotypic consequences. We show that trimethylated histone H3 lysine 9 (H3K9me3) is a major constituent of this imprint, and that stable propagation thereof is coupled to RNA interference (RNAi). Our findings reveal a distinct form of epigenetic memory in which fission yeast cells acquire heritable, transcriptionally active epialleles that confer gene silencing and manifest a phenotype only in particular, recurring situations. This demonstrates that epigenetic inheritance is adaptive and could potentially constitute a strategy to cope with adverse environmental conditions. If conserved in other eukaryotes, this phenomenon will impact our comprehension of natural variation and epigenetics in evolution.

Dataset Information

Inheritance of a Phenotypically Neutral Epimutation Evokes Gene Silencing in Later Generations.

Publications

Inheritance of a Phenotypically Neutral Epimutation Evokes Gene Silencing in Later Generations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets