Bespalova Alina V, Kulikova Dina A, Zelentsova Elena S, Rezvykh Alexander P, Guseva Iuliia O, Dorador Ana P, Evgen'ev Mikhail B, Funikov Sergei Y
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 119334 Moscow, Russia.
Int J Mol Sci. 2025 Apr 29;26(9):4243. doi: 10.3390/ijms26094243.
Piwi-interacting RNAs (piRNAs) play a crucial role in silencing transposable elements (TEs) in the germ cells of Metazoa by acting as sequence-specific guides. Originating from distinct genomic loci, called piRNA clusters, piRNA can trigger an epigenetic conversion of TE insertions into piRNA clusters by means of a paramutation-like process. However, the variability in piRNA clusters' capacity to induce such conversions remains poorly understood. Here, we investigated two strains with differing capacities to produce piRNAs from the subtelomeric and gene loci. We found that active piRNA generation correlates with high levels of the heterochromatic mark histone 3 lysine 9 trimethylation (H3K9me3) over genomic regions that give rise to piRNAs. Importantly, the maternal transmission of piRNAs drives their production in the progeny, even from homologous loci previously inactive in piRNA biogenesis. The locus, once epigenetically converted, maintained enhanced piRNA production in subsequent generations lacking the original allele carrying the active piRNA cluster. In contrast, piRNA expression from the converted locus was lost in offspring lacking the inducer allele. The present findings suggest that the paramutation-like behavior of piRNA clusters may be influenced not only by piRNAs but also by structural features and the chromatin environment in the proximity to telomeres, providing new insights into the epigenetic regulation of the Drosophila genome.
Piwi相互作用RNA（piRNA）通过作为序列特异性向导，在后生动物生殖细胞中转座元件（TE）的沉默过程中发挥关键作用。piRNA起源于称为piRNA簇的不同基因组位点，它可以通过类似副突变的过程触发TE插入到piRNA簇中的表观遗传转化。然而，piRNA簇诱导这种转化能力的变异性仍知之甚少。在这里，我们研究了两个从亚端粒和基因位点产生piRNA能力不同的品系。我们发现，活跃的piRNA产生与产生piRNA的基因组区域上高水平的异染色质标记组蛋白3赖氨酸9三甲基化（H3K9me3）相关。重要的是，piRNA的母系传递驱动其在后代中的产生，即使是来自以前在piRNA生物发生中不活跃的同源位点。该位点一旦发生表观遗传转化，在缺乏携带活跃piRNA簇的原始等位基因的后代中仍保持增强的piRNA产生。相比之下，在缺乏诱导等位基因的后代中，来自转化位点的piRNA表达会丢失。目前的研究结果表明，piRNA簇的类似副突变行为可能不仅受piRNA影响，还受端粒附近的结构特征和染色质环境影响，这为果蝇基因组的表观遗传调控提供了新的见解。
