Trans-generational inheritance of a phenotypically neutral epimutation enables descendants to reinstate an ancestral silencing episode
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ABSTRACT:
PROVIDER: PRJNA492871 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7894680.fastq.gz | Fastqsanger.gz | |||
| SRR7894690.fastq.gz | Fastqsanger.gz | |||
| SRR7894700.fastq.gz | Fastqsanger.gz | |||
| SRR7894710.fastq.gz | Fastqsanger.gz | |||
| SRR7894720.fastq.gz | Fastqsanger.gz |
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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.
2019-03-22 | GSE120352 | GEO
Project description: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.
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Project description:Mistakes in the maintenance of CG methylation is a source of heritable epimutations in plants. Multigenerational surveys indicate that the rate of these stochastic events varies substantially across the genome, with some regions harboring localized “epimutation hotspots”. Using Arabidopsis as a model, we show that epimutation hotspots are indexed by a specific set of chromatin states (CS) that map to sub-regions of gene body methylation genes. Although these regions comprise only ~12% of all CGs in the genome, they account for ~63% of all epimutation events per unit time. Molecular profiling revealed that these regions contain unique sequence features, harbor steady-state intermediate methylation levels, and act as putative targets of antagonistic DNA methylation pathways. We further demonstrate that experimentally-induced shifts in steady-state methylation in these hotspot regions are sufficient to significantly alter local epimutation intensities. Our work thus lays foundation for dissecting the molecular mechanisms of epimutation hotspots in plants.
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