Dynamic CpG island methylation landscape in oocytes and preimplantation embryos.
Dynamic CpG island methylation landscape in oocytes and preimplantation embryos.
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阐明CpG岛（CGIs）在生殖细胞中甲基化的方式和程度对于理解基因组印记和表观遗传重编程至关重要。在这里，我们提出了第一个综合的哺乳动物卵母细胞的表观基因组分析，确定超过一千CGIs甲基化成熟卵母细胞。我们发现这些CGI依赖于DNMT3A和DNMT3L，但在序列水平上并不明显，包括CpG周期。它们优先位于活性转录单位内，并且在H3K4me3中相对耗尽，支持甲基化的一般转录依赖性机制。很少有甲基化的CGIs被完全保护免于受精后重编程，但令人惊讶的是，大多数CGIs在E3.5囊胚中表现出不完全的去甲基化。我们的研究表明，配子中的CGI甲基化并不完全与基因组印记相关，但它是决定植入前胚胎甲基化状态的一个重要因素，这表明需要重新评估受精后去甲基化的机制。
Elucidating how and to what extent CpG islands (CGIs) are methylated in germ cells is essential to understand genomic imprinting and epigenetic reprogramming. Here, we present the first integrated epigenomic analysis of mammalian oocytes, identifying over a thousand CGIs methylated in mature oocytes. We show that these CGIs depend on DNMT3A and DNMT3L, but are not distinct at the sequence level, including in CpG periodicity. They are preferentially located within active transcription units and are relatively depleted in H3K4me3, supporting a general transcription-dependent mechanism of methylation. Very few methylated CGIs are fully protected from post-fertilisation reprogramming but, surprisingly, the majority exhibits incomplete demethylation in E3.5 blastocysts. Our study shows that CGI methylation in gametes is not entirely related to genomic imprinting, but is a strong factor in determining methylation status in preimplantation embryos, suggesting a need to reassess mechanisms of post-fertilization demethylation.
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