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Epigenetic transcriptional and phenotypic responses in two generations of Daphnia magna exposed to the DNA methylation inhibitor 5-azacytidine

机译:暴露于DNA甲基化抑制剂5-氮杂胞苷的两代水蚤的表观遗传转录和表型反应

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摘要

The water flea Daphnia magna is a keystone species in freshwater ecosystems and has been widely used as a model organism in environmental ecotoxicology. This aquatic crustacean is sensitive to environmental stressors and displays considerable plasticity in adapting to changing environmental conditions. Part of this plasticity may be due to epigenetic regulation of gene expression, including changes to DNA methylation and histone modifications. Because of the generally hypomethylated genome of this species, we hypothesized that the histone code may have an essential role in the epigenetic control and that histone modifications might be an early marker for stress. This study aims to characterize the epigenetic, transcriptional and phenotypic responses and their causal linkages in directly exposed adult (F0) Daphnia and peritoneal exposed neonates (F1) after a chronic (7-day) exposure to a sublethal concentration (10 mg/l) of 5-azacytidine, a well-studied vertebrate DNA methylation inhibitor. Exposure of the F0 generation significantly reduced the cumulative fecundity, accompanied with differential expression of genes in the one-carbon-cycle metabolic pathway. In the epigenome of the F0 generation, a decrease in global DNA methylation, but no significant changes on H3K4me3 or H3K27me3, were observed. In the F1 offspring generation, changes in gene expression, a significant reduction in global DNA methylation and changes in histone modifications were identified. The results indicate that exposure during adulthood may result in more pronounced effects on early development in the offspring generation, though interpretation of the data should be carefully done since both the exposure regime and developmental period is different in the two generations examined. The obtained results improve our understanding of crustacean epigenetics and the tools developed may promote use of epigenetic markers in hazard assessment of environmental stressors.
机译:蚤蚤(Daphnia magna)是淡水生态系统中的关键物种,已被广泛用作环境生态毒理学中的典范生物。这种水生甲壳动物对环境压力敏感,在适应不断变化的环境条件时显示出可塑性。这种可塑性的部分原因可能是由于基因表达的表观遗传调控,包括DNA甲基化的变化和组蛋白修饰。由于该物种的基因组通常发生甲基化,因此我们推测组蛋白编码可能在表观遗传控制中起重要作用,而组蛋白修饰可能是应激的早期标记。这项研究旨在表征在慢性(7天)暴露于亚致死浓度(10 mg / l)后直接暴露的成年(F0)水蚤和腹膜暴露的新生儿(F1)的表观遗传,转录和表型反应及其因果关系研究人员充分研究了5-氮杂胞苷的脊椎动物DNA甲基化抑制剂。暴露于F0代会显着降低累积繁殖力,并伴随一个碳循环代谢途径中基因的差异表达。在F0代的表观基因组中,总体DNA甲基化水平下降,但未观察到H3K4me3或H3K27me3的显着变化。在F1后代中,鉴定出基因表达的变化,总体DNA甲基化的显着降低以及组蛋白修饰的变化。结果表明,成年期的接触可能会对后代的早期发育产生更明显的影响,尽管对数据的解释应谨慎进行,因为所研究的两代接触方式和发育时期均不同。获得的结果提高了我们对甲壳动物表观遗传学的理解,开发的工具可能会促进表观遗传标记在环境胁迫源危害评估中的使用。

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