DNA methylation is an essential epigenetic mechanism that regulates cellular reprogramming and development. Studies using whole-genome bisulfite sequencing have revealed distinct DNA methylome landscapes in human and mouse cells and tissues. However, the factors responsible for the differences in megabase-scale methylome patterns between cell types remain poorly understood. By analyzing publicly available 258 human and 301 mouse whole-genome bisulfite sequencing datasets, we reveal that genomic regions rich in guanine and cytosine, when located near the nuclear center, are highly susceptible to both global DNA demethylation and methylation events during embryonic and germline reprogramming. Furthermore, we found that regions that generate partially methylated domains during global DNA methylation are more likely to resist global DNA demethylation, contain high levels of adenine and thymine, and are adjacent to the nuclear lamina. The spatial properties of genomic regions, influenced by their guanine-cytosine content, are likely to affect the accessibility of molecules involved in DNA (de)methylation. These properties shape megabase-scale DNA methylation patterns and change as cells differentiate, leading to the emergence of different megabase-scale methylome patterns across cell types.

中文翻译：

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时空 DNA 甲基化动态塑造了兆碱基规模的甲基化组景观。

DNA 甲基化是调节细胞重编程和发育的重要表观遗传机制。使用全基因组亚硫酸氢盐测序的研究揭示了人类和小鼠细胞和组织中独特的 DNA 甲基化景观。然而，导致细胞类型之间兆碱基级甲基化组模式差异的因素仍然知之甚少。通过分析公开的 258 个人类和 301 个小鼠全基因组亚硫酸氢盐测序数据集，我们揭示了富含鸟嘌呤和胞嘧啶的基因组区域，当位于核中心附近时，在胚胎和种系重编程过程中极易受到全局 DNA 去甲基化和甲基化事件的影响。此外，我们发现在整体DNA甲基化过程中产生部分甲基化结构域的区域更有可能抵抗整体DNA去甲基化，含有高水平的腺嘌呤和胸腺嘧啶，并且与核纤层相邻。基因组区域的空间特性受其鸟嘌呤-胞嘧啶含量的影响，可能会影响参与 DNA（去）甲基化的分子的可及性。这些特性塑造了兆碱基级 DNA 甲基化模式，并随着细胞分化而变化，导致不同细胞类型出现不同的兆碱基级甲基化模式。