Department of Neurobiology, Wise Faculty of Life Sciences & Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Elife. 2019 Mar 14;8:e40448. doi: 10.7554/eLife.40448.
In , RNA interference (RNAi) responses can transmit across generations via small RNAs. RNAi inheritance is associated with Histone-3-Lysine-9 tri-methylation (H3K9me3) of the targeted genes. In other organisms, maintenance of silencing requires a feed-forward loop between H3K9me3 and small RNAs. Here, we show that in not only is H3K9me3 unnecessary for inheritance, the modification's function depends on the identity of the RNAi-targeted gene. We found an asymmetry in the requirement for H3K9me3 and the main worm H3K9me3 methyltransferases, SET-25 and SET-32. Both methyltransferases promote heritable silencing of the foreign gene , but are dispensable for silencing of the endogenous gene . Genome-wide examination of heritable endogenous small interfering RNAs (endo-siRNAs) revealed that endo-siRNAs that depend on SET-25 and SET-32 target newly acquired and highly H3K9me3 marked genes. Thus, 'repressive' chromatin marks could be important specifically for heritable silencing of genes which are flagged as 'foreign', such as .
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在中，RNA 干扰 (RNAi) 反应可以通过小 RNA 在代际间传递。RNAi 遗传与靶基因的组蛋白 3-赖氨酸-9 三甲基化 (H3K9me3) 有关。在其他生物中，沉默的维持需要 H3K9me3 和小 RNA 之间的前馈环。在这里，我们表明，在中，H3K9me3 的修饰不仅对遗传是不必要的，而且其功能取决于 RNAi 靶向基因的身份。我们发现 H3K9me3 和主要的蠕虫 H3K9me3 甲基转移酶 SET-25 和 SET-32 的需求存在不对称性。这两种甲基转移酶都促进外源基因的可遗传沉默，但对内源基因的沉默是可有可无的。对可遗传的内源性小干扰 RNA (endo-siRNA) 的全基因组检查表明，依赖 SET-25 和 SET-32 的 endo-siRNA 靶向新获得的和高度 H3K9me3 标记的基因。因此，“抑制性”染色质标记可能对被标记为“外来”的基因的可遗传沉默特别重要，例如。
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