BACKGROUND Daphnia species reproduce by cyclic parthenogenesis involving both sexual and asexual reproduction. The sex of the offspring is environmentally determined and mediated via endocrine signalling by the mother. Interestingly, male and female Daphnia can be genetically identical, yet display large differences in behaviour, morphology, lifespan and metabolic activity. Our goal was to integrate multiple omics datasets, including gene expression, splicing, histone modification and DNA methylation data generated from genetically identical female and male Daphnia pulex under controlled laboratory settings with the aim of achieving a better understanding of the underlying epigenetic factors that may contribute to the phenotypic differences observed between the two genders. RESULTS In this study we demonstrate that gene expression level is positively correlated with increased DNA methylation, and histone H3 trimethylation at lysine 4 (H3K4me3) at predicted promoter regions. Conversely, elevated histone H3 trimethylation at lysine 27 (H3K27me3), distributed across the entire transcript length, is negatively correlated with gene expression level. Interestingly, male Daphnia are dominated with epigenetic modifications that globally promote elevated gene expression, while female Daphnia are dominated with epigenetic modifications that reduce gene expression globally. For examples, CpG methylation (positively correlated with gene expression level) is significantly higher in almost all differentially methylated sites in male compared to female Daphnia. Furthermore, H3K4me3 modifications are higher in male compared to female Daphnia in more than 3/4 of the differentially regulated promoters. On the other hand, H3K27me3 is higher in female compared to male Daphnia in more than 5/6 of differentially modified sites. However, both sexes demonstrate roughly equal number of genes that are up-regulated in one gender compared to the other sex. Since, gene expression analyses typically assume that most genes are expressed at equal level among samples and different conditions, and thus cannot detect global changes affecting most genes. CONCLUSIONS The epigenetic differences between male and female in Daphnia pulex are vast and dominated by changes that promote elevated gene expression in male Daphnia. Furthermore, the differences observed in both gene expression changes and epigenetic modifications between the genders relate to pathways that are physiologically relevant to the observed phenotypic differences.

中文翻译：

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表型上可区分的，遗传上相同的雌雄Daphnia pulex的综合表观基因组分析。

背景技术水蚤物种通过涉及性和无性繁殖的周期性孤雌生殖而繁殖。后代的性别是环境决定的，并由母亲通过内分泌信号传导介导。有趣的是，雄性和雌性水蚤在基因上可以相同，但在行为，形态，寿命和代谢活性方面却表现出很大差异。我们的目标是在受控的实验室环境下整合多个基因组学数据集，包括基因表达，剪接，组蛋白修饰和基因相同的雌雄Daphnia pulex产生的DNA甲基化数据，目的是更好地了解可能促成潜在的表观遗传因素观察到两种性别之间的表型差异。结果在这项研究中，我们证明基因表达水平与增加的DNA甲基化和预测的启动子区域的赖氨酸4（H3K4me3）处的组蛋白H3三甲基化呈正相关。相反，在整个转录物长度上分布的赖氨酸27（H3K27me3）处的组蛋白H3三甲基化升高与基因表达水平呈负相关。有趣的是，雄性水蚤以表观遗传修饰为主导，这种表观遗传修饰总体上促进了基因表达的升高，而雌性水蚤则以表观遗传修饰为主导，全局的表达水平降低了基因表达。例如，与雌性水蚤相比，雄性几乎所有差异甲基化位点中的CpG甲基化（与基因表达水平呈正相关）显着更高。此外，在超过3/4的差异调控启动子中，雄性H3K4me3修饰高于雌性水蚤。另一方面，在超过5/6的差异修饰位点中，雌性H3K27me3高于雄性水蚤。但是，两种性别都显示出与另一种性别相比，一种性别上调的基因数量大致相等。由于基因表达分析通常假设大多数基因在样品和不同条件下表达水平相同，因此无法检测到影响大多数基因的全局变化。结论水蚤的雄性和雌性之间的表观遗传差异很大，且以促进雄水蚤基因表达升高的变化为主。此外，