The establishment and maintenance of chromatin domains shape the epigenetic memory of a cell, with the methylation of histone H3 lysine 9 (H3K9me) defining transcriptionally silent heterochromatin. We show here that the C. elegans SET-25 (SUV39/G9a) histone methyltransferase (HMT), which catalyzes H3K9me1, me2 and me3, can establish repressed chromatin domains de novo, unlike the SETDB1 homolog MET-2. Thus, SET-25 is needed to silence novel insertions of RNA or DNA transposons, and repress tissue-specific genes de novo during development. We identify two partially redundant pathways that recruit SET-25 to its targets. One pathway requires LIN-61 (L3MBTL2), which uses its four MBT domains to bind the H3K9me2 deposited by MET-2. The second pathway functions independently of MET-2 and involves the somatic Argonaute NRDE-3 and small RNAs. This pathway targets primarily highly conserved RNA and DNA transposons. These redundant SET-25 targeting pathways (MET-2–LIN-61–SET-25 and NRDE-3–SET-25) ensure repression of intact transposons and de novo insertions, while MET-2 can act alone to repress simple and satellite repeats. Removal of both pathways in the met-2;nrde-3 double mutant leads to the loss of somatic H3K9me2 and me3 and the synergistic derepression of transposons in embryos, strongly elevating embryonic lethality.

中文翻译：

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Argonaute NRDE-3 和 MBT 域蛋白 LIN-61 冗余招募 H3K9me3 HMT 以防止胚胎致死和转座子表达

染色质结构域的建立和维持塑造了细胞的表观遗传记忆，组蛋白 H3 赖氨酸 9 (H3K9me) 的甲基化定义了转录沉默的异染色质。我们在这里展示了线虫SET-25 (SUV39/G9a) 组蛋白甲基转移酶 (HMT)，它催化 H3K9me1、me2 和 me3，可以从头建立抑制染色质域，与 SETDB1 同系物 MET-2 不同。因此，需要 SET-25 来沉默 RNA 或 DNA 转座子的新插入，并在发育过程中从头抑制组织特异性基因。我们确定了将 SET-25 招募到其目标的两个部分冗余的途径。一种途径需要 LIN-61 (L3MBTL2)，它使用其四个 MBT 域来结合 MET-2 存放的 H3K9me2。第二种途径独立于 MET-2 发挥作用，涉及体细胞 Argonaute NRDE-3 和小 RNA。该途径主要针对高度保守的 RNA 和 DNA 转座子。这些冗余的 SET-25 靶向通路（MET-2-LIN-61-SET-25 和 NRDE-3-SET-25）确保抑制完整转座子和从头插入，而 MET-2 可以单独作用抑制简单和卫星重复。去除met-2;nrde-3中的两条途径 双突变体导致体细胞 H3K9me2 和 me3 的丢失以及胚胎中转座子的协同去抑制，强烈提高胚胎致死率。