Hypoxia induces transgenerational epigenetic inheritance of small RNAs

缺氧诱导小RNA的跨代表观遗传

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作者:Simon Yuan Wang, Kathleen Kim, Zach Klapholz O'Brown, Aileen Levan, Anne Elizabeth Dodson, Scott G Kennedy, Chaim Chernoff, Eric Lieberman Greer

Abstract

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.

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