The histone demethylase Kdm3 prevents auto-immune piRNAs production in Drosophila

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 (BX2), 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 Kdm3 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., ,动物生殖系的基因组完整性可通过PIWI互作RNA（PIWI-interacting RNAs，piRNAs）抵御转座因子的活性。尽管piRNA的生物发生过程已得到深入探究，但人们对作为piRNA基因组来源的piRNA簇的遗传决定机制仍知之甚少。本研究利用一种具有双模态表观遗传状态的piRNA簇（BX2），鉴定出组蛋白去甲基化酶Kdm3能够抑制隐秘的piRNA生成。在Kdm3缺失的条件下，数十个包含编码基因的区域会转变为真正的生殖系双链piRNA簇。Kdm3突变雌性个体所产的卵，其发育缺陷表型与嵌入新增piRNA簇中的基因功能缺失所引发的表型完全一致，这提示功能性卵巢“自身免疫性”piRNAs可通过遗传传递。通过染色质修饰拮抗piRNA簇的确定过程，似乎对防止自身免疫性基因源性piRNA的生成至关重要。