The methylation of histone H3 at lysine 79 is a feature of open chromatin. It is deposited by the conserved histone methyltransferase DOT1. Recently, DOT1 localization and H3K79 methylation (H3K79me) have been correlated with enhancers in C. elegans and mammalian cells. Since earlier research implicated H3K79me in preventing heterochromatin formation both in yeast and leukemic cells, we sought to inquire whether a H3K79me deficiency would lead to higher levels of heterochromatic histone modifications, specifically H3K9me2, at developmental enhancers in C. elegans. Therefore, we used H3K9me2 ChIP-seq to compare its abundance in control and dot-1.1 loss-of-function mutant worms, as well as in rde-4; dot-1.1 and rde-1; dot-1.1 double mutants. The rde-1 and rde-4 genes are components of the RNAi pathway in C. elegans, and RNAi is known to initiate H3K9 methylation in many organisms, including C. elegans. We have previously shown that dot-1.1(−) lethality is rescued by rde-1 and rde-4 loss-of-function. Here we found that H3K9me2 was elevated in enhancer, but not promoter, regions bound by the DOT-1.1/ZFP-1 complex in dot-1.1(−) worms. We also found increased H3K9me2 at genes targeted by the ALG-3/4-dependent small RNAs and repeat regions. Our results suggest that ectopic H3K9me2 in dot-1.1(−) could, in some cases, be induced by small RNAs.

中文翻译：

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缺乏 DOT-1.1 的秀丽隐杆线虫在增强子和某些 RNAi 调节区域显示 H3K9me2 增加。

组蛋白 H3 在第 79 位赖氨酸的甲基化是开放染色质的一个特征。它由保守的组蛋白甲基转移酶 DOT1 沉积。最近，DOT1 定位和 H3K79 甲基化 (H3K79me) 与秀丽隐杆线虫和哺乳动物细胞中的增强子相关。由于早期研究表明 H3K79me 与防止酵母和白血病细胞中的异染色质形成有关，我们试图探究 H3K79me 缺陷是否会导致更高水平的异染色质组蛋白修饰，特别是 H3K9me2，在秀丽隐杆线虫的发育增强子中。因此，我们使用 H3K9me2 ChIP-seq 来比较其在对照和dot-1.1功能丧失突变体蠕虫以及rde-4 中的丰度；点 1.1和rde-1; dot-1.1双突变体。rde -1和rde-4基因是秀丽隐杆线虫中 RNAi 通路的组成部分，并且已知 RNAi 在包括秀丽隐杆线虫在内的许多生物体中启动 H3K9 甲基化。我们之前已经证明dot-1.1(−)致死率是由rde-1和rde-4功能丧失挽救的。在这里，我们发现 H3K9me2 在增强子中升高，但不是启动子，由dot-1.1(−)蠕虫中的 DOT-1.1/ZFP-1 复合体结合的区域。我们还发现 ALG-3/4 依赖性小 RNA 和重复区域靶向的基因中 H3K9me2 增加。我们的结果表明dot-1.1(−)中的异位 H3K9me2在某些情况下，可以由小 RNA 诱导。