Environmentally-induced epigenetic conversion of a piRNA cluster

Abstract

Transposable element (TE) activity is repressed in animal gonads by PIWI-interacting RNAs (piRNAs) produced by piRNA clusters. Current models in flies propose that germinal piRNA clusters are functionally defined by the maternal inheritance of piRNAs produced during the previous generation. Taking advantage of an inactive, but ready to go, cluster of P-element derived transgene insertions in Drosophila melanogaster, we show here that raising flies at high temperature (29°C) instead of 25°C triggers the stable conversion of this locus from inactive into actively producing functional piRNAs. The increase of antisense transcripts from the cluster at 29°C combined with the requirement of transcription of euchromatic homologous sequences, suggests a role of double stranded RNA in the production of de novo piRNAs. This report describes the first case of the establishment of an active piRNA cluster by environmental changes in the absence of maternal inheritance of homologous piRNAs.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

Epigenetic Requirements for Triggering Heterochromatinization and Piwi-Interacting RNA Production from Transgenes in the Drosophila Germline

“…One could argue that initially, the chromatin structure and piRNA production from the I-transgenes in all strains were the same, although later, in the course of the strain-specific history, the transgenes in the 2.1 s and 2.4 s strains became stronger, which resulted in higher Rhi occupancy and more efficient piRNA production. This could have happened, for example, as a result of the increase in temperature or ageing − epigenetic factors, which are known to affect the transcription of piRNA clusters and the accumulation of piRNAs [41][42][43]. The I-transgenes in the 1.9 w and 3.6 w strains did not demonstrate efficient piRNA production, possibly due to the strain-specific epigenetic history.…”

Environmentally-Induced Transgenerational Epigenetic Inheritance: Implication of PIWI Interacting RNAs

“…For instance, in rat sperm, vinclozolin or DDT pesticide exposure modifies DNA methylation, drives histone retention, and decreases the global number of expressed small non-coding RNAs (miRNA, piRNAs, and tsRNAs) and long non-coding RNAs, affecting expression of genes implicated in metabolism, signaling, and transcription [20,21] and is correlated with the occurrence of several pathologies [22,23,24,25]. In Drosophila , the elevation of temperature during development causes functional piRNA emergence associated with H3K9me3 enrichment from a particular repeated locus mimicking a piRNA cluster for over 50 generations [26] (Table 1). Such cross-talk between several epigenetic modifications is not restricted to animals.…”

“…This new epigenetic state, sensitive to the H3K9 methyltransferase mutant, can then be maintained up to 32 generations [27]. Taken together, H3K9me3 marks and small non-coding RNA could act together to reinforce epigenetic stability through generations thanks to a feedback loop: on the one hand, H3K9me3 leads to heterochromatin formation and recruits the RNAi machinery, and on the other hand, the RNAi machinery targets H3K9 residues and induces their trimethylation [26,27].…”

Mechanisms of epigenetic inheritance of variable traits through the germline

“…The active epialleles produce piRNAs and repress homologous loci in trans, while the silent epialleles do not (de Vanssay et al 2012). The silent transgenic piRNA-producing epialleles can become activated by exposure to high temperature and this temperature-induced activity state can be inherited (Casier et al 2019). It should be noted that temperatureinduced activation has only been observed at transgenic piRNA-producing loci (Casier et al 2019) and may not reflect a natural mechanism of defence against transposon activation upon exposure to increased temperature.…”