A transgenerational role of the germline nuclear RNAi pathway in repressing heat stress-induced transcriptional activation in C. elegans.
A transgenerational role of the germline nuclear RNAi pathway in repressing heat stress-induced transcriptional activation in C. elegans.
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DOI：
10.1186/s13072-016-0052-x
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发表时间：
2016
影响因子：
3.9
通讯作者：
Gu SG
中科院分区：
文献类型：
--
作者：
Ni JZ;Kalinava N;Chen E;Huang A;Trinh T;Gu SG
环境应激诱导的跨代表观遗传效应已在多种模式生物和人类中观察到。人们对这种现象的能力和机制知之甚少。在秀丽隐杆线虫中，siRNA通过种系核RNAi途径介导跨代基因沉默。当秀丽隐杆线虫处于热应激状态时，这一途径也是维持种系不朽所必需的。然而，潜在的分子机制尚不清楚。在这项研究中，我们在全基因组水平上研究了热应激对染色质、转录和sirna的影响，以及在野生型或种系核RNAi突变动物中，热诱导的影响是否具有跨代遗传性。我们使用野生型秀丽隐杆线虫和缺乏种系特异性核Argonaute蛋白HRDE-1/WAGO-9的突变株进行了12代温度转移实验。通过在全基因组水平上检测mRNA、小RNA、RNA聚合酶II和H3K9三甲基化谱，我们揭示了HRDE-1在抑制热应激诱导的280多个基因转录激活中的表观遗传作用。这些基因中有许多位于LTR（长端重复）逆转录转座子内或附近。引人注目的是，对于这些基因中的一些，在热应激下hrde-1突变体中，热应激诱导的转录激活在后期代中加强，并且在突变动物移回较低温度后至少可遗传两代。hrde-1突变也会导致许多基因的siRNA表达改变。这种对siRNA的影响取决于温度和生成。我们的研究表明，秀丽隐杆线虫种系核RNAi途径的大量内源性靶点对热诱导的转录激活敏感。包括LTR反转录转座子在内的某些基因组位点的这种效应是跨代的。种系核RNAi在转录水平上拮抗这种温度效应，因此可能在秀丽隐杆线虫的热应激反应中起关键作用。本文的在线版本（doi:10.1186/s13072-016-0052-x）包含补充材料，可供授权用户使用。
Environmental stress-induced transgenerational epigenetic effects have been observed in various model organisms and human. The capacity and mechanism of such phenomena are poorly understood. In C. elegans, siRNA mediates transgenerational gene silencing through the germline nuclear RNAi pathway. This pathway is also required to maintain the germline immortality when C. elegans is under heat stress. However, the underlying molecular mechanism is unknown. In this study, we investigated the impact of heat stress on chromatin, transcription, and siRNAs at the whole-genome level, and whether any of the heat-induced effects is transgenerationally heritable in either the wild-type or the germline nuclear RNAi mutant animals. We performed 12-generation temperature-shift experiments using the wild-type C. elegans and a mutant strain that lacks the germline-specific nuclear Argonaute protein HRDE-1/WAGO-9. By examining the mRNA, small RNA, RNA polymerase II, and H3K9 trimethylation profiles at the whole-genome level, we revealed an epigenetic role of HRDE-1 in repressing heat stress-induced transcriptional activation of over 280 genes. Many of these genes are in or near LTR (long-terminal repeat) retrotransposons. Strikingly, for some of these genes, the heat stress-induced transcriptional activation in the hrde-1 mutant intensifies in the late generations under the heat stress and is heritable for at least two generations after the mutant animals are shifted back to lower temperature. hrde-1 mutation also leads to siRNA expression changes of many genes. This effect on siRNA is dependent on both the temperature and generation. Our study demonstrated that a large number of the endogenous targets of the germline nuclear RNAi pathway in C. elegans are sensitive to heat-induced transcriptional activation. This effect at certain genomic loci including LTR retrotransposons is transgenerational. Germline nuclear RNAi antagonizes this temperature effect at the transcriptional level and therefore may play a key role in heat stress response in C. elegans. The online version of this article (doi:10.1186/s13072-016-0052-x) contains supplementary material, which is available to authorized users.