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首页> 外文期刊>Epigenetics & Chromatin >A transgenerational role of the germline nuclear RNAi pathway in repressing heat stress-induced transcriptional activation in C. elegans
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A transgenerational role of the germline nuclear RNAi pathway in repressing heat stress-induced transcriptional activation in C. elegans

机译：种系核RNAi途径在抑制线虫中热应激诱导的转录激活中的跨代作用

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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.
机译：在各种模型生物和人类中都观察到环境胁迫引起的跨代表观遗传效应。对这种现象的能力和机理了解甚少。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胁迫下时，也需要该途径来维持种系永生。但是，潜在的分子机制尚不清楚。在这项研究中，我们研究了热应激在全基因组水平上对染色质，转录和siRNA的影响，以及在野生型或种系核RNAi突变动物中，是否有任何热诱导效应可遗传传代。 。我们使用野生型秀丽隐杆线虫和缺乏种系特异性核Argonaute蛋白质HRDE-1 / WAGO-9的突变株进行了12代温度转变实验。通过检查全基因组水平的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多个基因的转录激活中的表观遗传学作用。这些基因中的许多在LTR（长末端重复）逆转座子中或附近。令人惊讶的是，对于其中的某些基因，hrde-1突变体中热应激诱导的转录激活在热应激下的后期世代会增强，并且在突变动物转回较低温度后至少可遗传两代。 hrde-1突变还导致许多基因的siRNA表达变化。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标对热诱导的转录激活敏感。在某些基因组基因座（包括LTR反转录转座子）上的这种效应是转基因的。生殖细胞核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。

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