PIWI-interacting RNAs (piRNAs) are germline-specific small RNAs that form effector complexes with PIWI proteins (Piwi–piRNA complexes) and play critical roles for preserving genomic integrity by repressing transposable elements (TEs). Drosophila Piwi transcriptionally silences specific targets through heterochromatin formation and increases histone H3K9 methylation (H3K9me3) and histone H1 deposition at these loci, with nuclear RNA export factor variant Nxf2 serving as a co-factor. Using ChEP and DamID-seq, we now uncover a Piwi/Nxf2-dependent target association with nuclear lamins. Hi-C analysis of Piwi or Nxf2-depleted cells reveals decreased intra-TAD and increased inter-TAD interactions in regions harboring Piwi–piRNA target TEs. Using a forced tethering system, we analyze the functional effects of Piwi–piRNA/Nxf2-mediated recruitment of piRNA target regions to the nuclear periphery. Removal of active histone marks is followed by transcriptional silencing, chromatin conformational changes, and H3K9me3 and H1 association. Our data show that the Piwi–piRNA pathway can induce stepwise changes in nuclear architecture and chromatin state at target loci for transcriptional silencing.

中文翻译：

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Piwi-piRNA 复合物诱导靶位点核结构的逐步变化

PIWI 相互作用 RNA (piRNA) 是种系特异性小 RNA，可与 PIWI 蛋白形成效应复合物（Piwi-piRNA 复合物），并通过抑制转座因子 (TE) 来保持基因组完整性。果蝇Piwi 通过异染色质形成转录沉默特定目标，并增加组蛋白 H3K9 甲基化 (H3K9me3) 和组蛋白 H1 在这些位点的沉积，核 RNA 输出因子变体 Nxf2 作为辅助因子。使用 ChEP 和 DamID-seq，我们现在发现了一个依赖于 Piwi/Nxf2 的靶标与核纤层蛋白的关联。Piwi 或 Nxf2 耗尽细胞的 Hi-C 分析显示，在含有 Piwi-piRNA 靶标 TE 的区域中，TAD 内相互作用减少，TAD 间相互作用增加。使用强制束缚系统，我们分析了 Piwi-piRNA/Nxf2 介导的 piRNA 目标区域向核外围募集的功能影响。去除活性组蛋白标记之后是转录沉默、染色质构象变化以及 H3K9me3 和 H1 关联。