Preimplantation embryos experience profound resetting of epigenetic information inherited from the gametes. Genome-wide analysis at single-base resolution has shown similarities but also species differences between human and mouse preimplantation embryos in DNA methylation patterns and reprogramming. Here, we have extended such analysis to two key livestock species, the pig and the cow. We generated genome-wide DNA methylation and whole-transcriptome datasets from gametes to blastocysts in both species. In oocytes from both species, a distinctive bimodal methylation landscape is present, with hypermethylated domains prevalent over hypomethylated domains, similar to human, while in the mouse the proportions are reversed.An oocyte-like pattern of methylation persists in the cleavage stages, albeit with some reduction in methylation level, persisting to blastocysts in cow, while pig blastocysts have a highly hypomethylated landscape. In the pig, there was evidence of transient de novo methylation at the 8-16 cell stages of domains unmethylated in oocytes, revealing a complex dynamic of methylation reprogramming. The methylation datasets were used to identify germline differentially methylated regions (gDMRs) of known imprinted genes and for the basis of detection of novel imprinted loci. Strikingly in the pig, we detected a consistent reduction in gDMR methylation at the 8-16 cell stages, followed by recovery to the blastocyst stage, suggesting an active period of imprint stabilization in preimplantation embryos. Transcriptome analysis revealed absence of expression in oocytes of both species of ZFP57, a key factor in the mouse for gDMR methylation maintenance, but presence of the alternative imprint regulator ZNF445. In conclusion, our study reveals species differences in DNA methylation reprogramming and suggests that porcine or bovine models may be closer to human in key aspects than in the mouse model.

中文翻译：

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植入前发育过程中的 DNA 甲基化变化揭示了印迹基因的种间差异和重编程事件。

植入前胚胎经历了从配子继承的表观遗传信息的深刻重置。单碱基分辨率下的全基因组分析显示了人类和小鼠植入前胚胎在 DNA 甲基化模式和重编程方面的相似性和物种差异。在这里，我们将这种分析扩展到两个关键的牲畜物种，猪和牛。我们在两个物种中生成了从配子到囊胚的全基因组 DNA 甲基化和全转录组数据集。在这两个物种的卵母细胞中，存在独特的双峰甲基化景观，高甲基化结构域普遍存在于低甲基化结构域上，与人类相似，而在小鼠中，比例相反。卵母细胞样的甲基化模式在卵裂阶段持续存在，尽管甲基化水平有所降低，持续到牛的囊胚，而猪的囊胚具有高度低甲基化的景观。在猪中，有证据表明在卵母细胞中未甲基化结构域的 8-16 个细胞阶段发生了瞬时从头甲基化，揭示了甲基化重编程的复杂动态。甲基化数据集用于识别已知印迹基因的种系差异甲基化区域 (gDMR)，并作为检测新印迹基因座的基础。令人惊讶的是，我们在猪的 8-16 细胞阶段检测到 gDMR 甲基化持续减少，随后恢复到囊胚阶段，表明植入前胚胎中存在印记稳定的活跃期。转录组分析显示两种 ZFP57 的卵母细胞均不表达，这是小鼠 gDMR 甲基化维持的关键因素，但存在替代压印调节器 ZNF445。总之，我们的研究揭示了 DNA 甲基化重编程的物种差异，并表明猪或牛模型在关键方面可能比小鼠模型更接近人类。