Chow Yit-Lai, Sato Fumihiko
Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Genes Cells. 2019 Jan;24(1):70-81. doi: 10.1111/gtc.12657. Epub 2018 Dec 21.
Epigenetic mechanisms allow for transgenerational memory of an ancestor's environment and can affect the gene expression, physiology and phenotype of that ancestor's descendants, independent of DNA sequence alteration. Among many model organisms, Caenorhabditis elegans has been instrumental in studies of transgenerational inheritance, most of which have focused on the effects of external stressors of the parent worm on the life span and stress resistance of future generations. In this work, we used Nile red staining of accumulated lipids in C. elegans to investigate the transgenerational effect of two benzylisoquinoline alkaloids, namely, berberine and sanguinarine. Our results showed that a reduction in Nile red fluorescence can be propagated to subsequent worm generations. Using mutant worms, we found that the transgenerational effect requires the ASH-2 component of the histone H3K4me3 complex and the HRDE-1 worm Argonaute protein. Ash-2 is also required for transgenerational inheritance of the xenobiotic response in the worm. Our study offers new insights into transmissible drug effects across multiple generations and suggests the importance of such analyses in the drug development process.
表观遗传机制能够实现对祖先环境的跨代记忆，并可影响该祖先后代的基因表达、生理机能和表型，而与DNA序列改变无关。在众多模式生物中，秀丽隐杆线虫在跨代遗传研究中发挥了重要作用，其中大部分研究聚焦于亲代线虫的外部应激源对后代寿命和抗逆性的影响。在这项研究中，我们利用尼罗红对秀丽隐杆线虫中积累的脂质进行染色，以研究两种苄基异喹啉生物碱（即小檗碱和血根碱）的跨代效应。我们的结果表明，尼罗红荧光的降低能够传递到后续的线虫世代。通过使用突变线虫，我们发现这种跨代效应需要组蛋白H3K4me3复合体的ASH-2组分以及线虫AGO蛋白HRDE-1。Ash-2对于线虫对外源生物反应的跨代遗传也是必需的。我们的研究为多代间可传递的药物效应提供了新的见解，并表明此类分析在药物研发过程中的重要性。
