RNAi-dependent heterochromatin assembly in fission yeast Schizosaccharomyces pombe requires heat-shock molecular chaperones Hsp90 and Mas5.
RNAi-dependent heterochromatin assembly in fission yeast Schizosaccharomyces pombe requires heat-shock molecular chaperones Hsp90 and Mas5.
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DOI：
10.1186/s13072-018-0199-8
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发表时间：
2018-06-04
影响因子：
3.9
通讯作者：
Urano T
中科院分区：
文献类型：
--
作者：
Okazaki K;Kato H;Iida T;Shinmyozu K;Nakayama JI;Murakami Y;Urano T
热休克分子伴侣蛋白 (Hsps) 促进小干扰 RNA (siRNA) 加载到 RNA 干扰 (RNAi) 效应复合物上。虽然RNAi过程与几种模式生物中的异染色质组装相结合，但热休克蛋白是否有助于表观遗传基因调控仍不清楚。在本研究中，我们使用裂殖酵母粟酒裂殖酵母作为模式生物，研究了 Hsp90 和 Mas5（核胞质 I 型 Hsp40 蛋白）在 RNAi 依赖性异染色质组装中的作用。通过基因筛选和生化分析，我们确定 Hsp90 和 Mas5 是新型沉默因子。编码这些因子的基因突变导致着丝粒周围的沉默去抑制，其中异染色质以RNAi依赖性方式组装，但不引起亚端粒的沉默，而亚端粒中RNAi是可有可无的。这些突变还导致着丝粒周围 Lys9 处组蛋白 H3 的二甲基化水平大幅降低，Argonaute 蛋白 Ago1 的关联也被取消。一致地，在这些突变细胞中检测不到与着丝粒周围重复相对应的siRNA。此外，Tas3（RNA 诱导的转录沉默复合物中的一种蛋白质）与 Ago1 的水平在 Mas5 缺失的情况下降低。我们的结果表明 Hsps Hsp90 和 Mas5 有助于 RNAi 依赖性异染色质组装。特别是，Mas5 似乎是体内稳定 Tas3 所必需的。我们推断 Hsp90 和 Hsp40 的损伤也可能影响其他生物体表观基因组的完整性。本文的在线版本 (10.1186/s13072-018-0199-8) 包含补充材料，可供授权用户使用。
Heat-shock molecular chaperone proteins (Hsps) promote the loading of small interfering RNA (siRNA) onto RNA interference (RNAi) effector complexes. While the RNAi process is coupled with heterochromatin assembly in several model organisms, it remains unclear whether the Hsps contribute to epigenetic gene regulation. In this study, we used the fission yeast Schizosaccharomyces pombe as a model organism and investigated the roles of Hsp90 and Mas5 (a nucleocytoplasmic type-I Hsp40 protein) in RNAi-dependent heterochromatin assembly. Using a genetic screen and biochemical analyses, we identified Hsp90 and Mas5 as novel silencing factors. Mutations in the genes encoding these factors caused derepression of silencing at the pericentromere, where heterochromatin is assembled in an RNAi-dependent manner, but not at the subtelomere, where RNAi is dispensable. The mutations also caused a substantial reduction in the level of dimethylation of histone H3 at Lys9 at the pericentromere, where association of the Argonaute protein Ago1 was also abrogated. Consistently, siRNA corresponding to the pericentromeric repeats was undetectable in these mutant cells. In addition, levels of Tas3, which is a protein in the RNA-induced transcriptional silencing complex along with Ago1, were reduced in the absence of Mas5. Our results suggest that the Hsps Hsp90 and Mas5 contribute to RNAi-dependent heterochromatin assembly. In particular, Mas5 appears to be required to stabilize Tas3 in vivo. We infer that impairment of Hsp90 and Hsp40 also may affect the integrity of the epigenome in other organisms. The online version of this article (10.1186/s13072-018-0199-8) contains supplementary material, which is available to authorized users.
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影响因子：
13.8
作者：
Craig EA;Marszalek J
通讯作者：
Marszalek J
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Jia, ST;Noma, K;Grewal, SIS
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Grewal, SIS
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Kagansky, Alexander;Folco, Hernan Diego;Allshire, Robin C.
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Dereeper A;Guignon V;Blanc G;Audic S;Buffet S;Chevenet F;Dufayard JF;Guindon S;Lefort V;Lescot M;Claverie JM;Gascuel O
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Gascuel O
影响因子：
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作者：
Bayne EH;Bijos DA;White SA;de Lima Alves F;Rappsilber J;Allshire RC
通讯作者：
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