Sormani Giulia, Haerter Jan O, Lövkvist Cecilia, Sneppen Kim
Center for Models of Life, Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark.
Mol Biosyst. 2016 Jun 21;12(7):2142-6. doi: 10.1039/c6mb00044d.
DNA methylation of CpG sites is an important epigenetic mark in mammals. Active promoters are often associated with unmethylated CpG sites, whereas methylated CpG sites correlate with silenced promoters. Methylation of CpG sites must be generally described as a dynamical process that is mediated by methylation enzymes, such as DNMT1 and DNMT3a/b. However, there are several models of how CpG sites can be protected from methylation and thereby remain unmethylated. In this paper we examine the combination of both: the positive feedbacks of DNA methylation and a short range counterpart which in turn protects-and thereby maintains-the unmethylated state. The emergent dynamics is provided by collaborative, re-enforcing feedbacks in favor of methylated CpG islands and cooperative protection of one CpG site by another in favor of unmethylated CpG sites. Our results suggest that this synthesis of mechanisms provides equally robust maintenance of both the unmethylated and methylated states of CpG islands.
CpG位点的DNA甲基化是哺乳动物中一种重要的表观遗传标记。活跃的启动子通常与未甲基化的CpG位点相关联，而甲基化的CpG位点则与沉默的启动子相关。CpG位点的甲基化通常必须被描述为由甲基化酶（如DNMT1和DNMT3a/b）介导的动态过程。然而，存在几种关于CpG位点如何免受甲基化从而保持未甲基化状态的模型。在本文中，我们研究了两者的结合：DNA甲基化的正反馈以及一种短程对应机制，该机制反过来保护并因此维持未甲基化状态。这种新兴动力学是由有利于甲基化CpG岛的协同、增强反馈以及一个CpG位点对另一个CpG位点的协同保护（有利于未甲基化的CpG位点）提供的。我们的结果表明，这种机制的综合作用能够同样稳健地维持CpG岛的未甲基化和甲基化状态。
