Nucleotide distance influences co-methylation between nearby CpG sites

Nucleotide distance influences co-methylation between nearby CpG sites
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DOI:
10.1016/j.ygeno.2019.05.007
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发表时间:
2020-01-01
期刊:
影响因子:
4.4
通讯作者:
Cocozza, Sergio
Cocozza, Sergio
中科院分区:
生物学3区
文献类型:
--
作者:
Affinito, Ornella;Palumbo, Domenico;Cocozza, Sergio

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单个CpG位点的甲基化倾向是独特的、非随机的,并且在整个基因组中都受到很好的调控。我们通过对人、小鼠和斑马鱼基因进行超深度靶向甲基化分析,研究了影响CPGS甲基化的结构和空间因素。我们发现甲基化不是一个随机的过程,邻近的CpG位点更有可能具有相同的甲基化状态。此外,如果CPGS之间的距离增加,则共甲基化程度降低。我们建立了一个模拟模型来分析本征磁化率和距离效应对CpG甲基化概率的贡献。我们的发现表明,特定甲基化模式的建立遵循一个普遍规则,必须考虑到这两个主要因素的协同和动态相互作用:特定CpG的内在甲基化敏感性和两个CpG位点之间的核苷酸距离。
The tendency of individual CpG sites to be methylated is distinctive, non-random and well-regulated throughout the genome. We investigated the structural and spatial factors influencing CpGs methylation by performing an ultra-deep targeted methylation analysis on human, mouse and zebrafish genes. We found that methylation is not a random process and that closer neighboring CpG sites are more likely to share the same methylation status. Moreover, if the distance between CpGs increases, the degree of co-methylation decreases. We set up a simulation model to analyze the contribution of both the intrinsic susceptibility and the distance effect on the probability of a CpG to be methylated. Our finding suggests that the establishment of a specific methylation pattern follows a universal rule that must take into account of the synergistic and dynamic interplay of these two main factors: the intrinsic methylation susceptibility of specific CpG and the nucleotide distance between two CpG sites.