Histone H3K36 trimethylation is essential for multiple silencing mechanisms in fission yeast.
Histone H3K36 trimethylation is essential for multiple silencing mechanisms in fission yeast.
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DOI：
10.1093/nar/gkw008
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发表时间：
2016-05-19
影响因子：
14.9
通讯作者：
Murakami Y
中科院分区：
文献类型：
--
作者：
Suzuki S;Kato H;Suzuki Y;Chikashige Y;Hiraoka Y;Kimura H;Nagao K;Obuse C;Takahata S;Murakami Y
在芽殖酵母中，Set2 通过 Set2-Rpb1 相互作用 (SRI) 结构域与 Ser2 和 Ser5 (CTD-S2,5-P) 磷酸化的 RNA 聚合酶 II (Pol2) 的 C 末端重复序列之间的相互作用，催化 H3K36（H3K36me2 和 H3K36me3）的二甲基化和三甲基化。 H3K36me2 足以招募 Rpd3S 组蛋白脱乙酰酶复合物来抑制转录区域的隐性转录。在裂殖酵母中，Set2 还负责 H3K36 甲基化，它至少部分通过募集 Clr6 复合物 II（Rpd3S 的同源物）来抑制 RNA 子集，包括异染色质和亚端粒 RNA。在这里，我们表明裂殖酵母 Set2 与 Pol2 通过 SRI 结构域的 CTD-S2P 依赖性相互作用是形成 H3K36me3 所必需的，但不是 H3K36me2 的形成。 H3K36me3 主要分别通过转录后和转录机制沉默异染色质和亚端粒转录本，而 H3K36me2 不足以沉默。 Clr6 复合物 II 似乎与 H3K36me3 的异染色质沉默无关。我们的结果表明，H3K36 甲基化在裂殖酵母中具有多个输出；这些发现为了解 H3K36 甲基化在后生动物中的独特作用提供了见解，后生动物具有不同的合成 H3K36me1/2 和 H3K36me3 的酶。
In budding yeast, Set2 catalyzes di- and trimethylation of H3K36 (H3K36me2 and H3K36me3) via an interaction between its Set2–Rpb1 interaction (SRI) domain and C-terminal repeats of RNA polymerase II (Pol2) phosphorylated at Ser2 and Ser5 (CTD-S2,5-P). H3K36me2 is sufficient for recruitment of the Rpd3S histone deacetylase complex to repress cryptic transcription from transcribed regions. In fission yeast, Set2 is also responsible for H3K36 methylation, which represses a subset of RNAs including heterochromatic and subtelomeric RNAs, at least in part via recruitment of Clr6 complex II, a homolog of Rpd3S. Here, we show that CTD-S2P-dependent interaction of fission yeast Set2 with Pol2 via the SRI domain is required for formation of H3K36me3, but not H3K36me2. H3K36me3 silenced heterochromatic and subtelomeric transcripts mainly through post-transcriptional and transcriptional mechanisms, respectively, whereas H3K36me2 was not enough for silencing. Clr6 complex II appeared not to be responsible for heterochromatic silencing by H3K36me3. Our results demonstrate that H3K36 methylation has multiple outputs in fission yeast; these findings provide insights into the distinct roles of H3K36 methylation in metazoans, which have different enzymes for synthesis of H3K36me1/2 and H3K36me3.