Hypoxia induces transgenerational epigenetic inheritance of small RNAs.
Hypoxia induces transgenerational epigenetic inheritance of small RNAs.
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DOI：
10.1016/j.celrep.2022.111800
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发表时间：
2022-12-13
期刊：
影响因子：
8.8
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中科院分区：
文献类型：
--
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动物感知并适应氧气供应的减少，但祖先的缺氧暴露是否以及如何引起正常缺氧饲养的后代的表型后果尚不清楚。我们表明，缺氧会导致线虫的脂质代际降低和生殖能力的跨代降低。这些表观遗传表型的传递依赖于抑制性组蛋白修饰酶和argonaute HRDE-1。喂食从缺氧处理的线虫中提取的小rna足以诱导生殖力缺陷。此外，内源性小干扰RNA F44E5.4/5在缺氧条件下的代际表达上调，用F44E5.4/5双链RNA （dsRNA）浸泡正常缺氧条件下饲养的秀丽隐杆线虫足以诱导代际生育缺陷。最后，我们证明了标记的F44E5.4/5 dsRNA本身是由父母传给孩子的。我们的研究结果表明，小rna对环境有反应，足以将父母的非遗传信息传递给他们天真的孩子。Wang等人发现，缺氧诱导蠕虫脂质降低和生育能力的表观遗传，这依赖于小rna和抑制性染色质修饰。他们表明，小rna足以诱导遗传性生育能力下降，并在几代之间追踪标记的内源性dsRNA。
Animals sense and adapt to decreased oxygen availability, but whether and how hypoxia exposure in ancestors can elicit phenotypic consequences in normoxia-reared descendants are unclear. We show that hypoxia educes an intergenerational reduction in lipids and a transgenerational reduction in fertility in the nematode Caenorhabditis elegans. The transmission of these epigenetic phenotypes is dependent on repressive histone-modifying enzymes and the argonaute HRDE-1. Feeding naive C. elegans small RNAs extracted from hypoxia-treated worms is sufficient to induce a fertility defect. Furthermore, the endogenous small interfering RNA F44E5.4/5 is upregulated intergenerationally in response to hypoxia, and soaking naive normoxia-reared C. elegans with F44E5.4/5 double-stranded RNA (dsRNA) is sufficient to induce an intergenerational fertility defect. Finally, we demonstrate that labeled F44E5.4/5 dsRNA is itself transmitted from parents to children. Our results suggest that small RNAs respond to the environment and are sufficient to transmit non-genetic information from parents to their naive children. Wang et al. find that hypoxia induces epigenetic inheritance of reduced lipids and fertility in worms and that this is dependent on small RNAs and repressive chromatin modifications. They show that small RNAs are sufficient to induce heritable fertility reductions and track a labeled endogenous dsRNA across generations.
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