The histone demethylase Kdm3 prevents auto-immune piRNAs production in <i>Drosophila</i>.

Casier, Karine; Autaa, Julie; Gueguen, Nathalie; Delmarre, Valérie; Marie, Pauline P; Ronsseray, Stéphane; Carré, Clément; Brasset, Emilie et al. · Sci Adv · 2023

basic_science · Level V

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Abstract

Genome integrity of the animal germline is protected from transposable element activity by PIWI-interacting RNAs (piRNAs). While piRNA biogenesis is intensively explored, little is known about the genetical determination of piRNA clusters, the genomic sources of piRNAs. Using a bimodal epigenetic state piRNA cluster (<i>BX2</i>), we identified the histone demethylase Kdm3 as being able to prevent a cryptic piRNA production. In the absence of Kdm3, dozens of coding gene-containing regions become genuine germline dual-strand piRNA clusters. Eggs laid by <i>Kdm3</i> mutant females show developmental defects phenocopying loss of function of genes embedded into the additional piRNA clusters, suggesting an inheritance of functional ovarian "auto-immune" piRNAs. Antagonizing piRNA cluster determination through chromatin modifications appears crucial to prevent auto-immune genic piRNAs production.

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