Epigenetic memory via concordant DNA methylation is inversely correlated to developmental potential of mammalian cells

In storing and transmitting epigenetic information, organisms must balance the need to maintain information about past conditions with the capacity to respond to information in their current and future environments. Some of this information is encoded by DNA methylation, which can be transmitted with variable fidelity from parent to daughter strand. High fidelity confers strong pattern matching between the strands of individual DNA molecules and thus pattern stability over rounds of DNA replication; lower fidelity confers reduced pattern matching, and thus greater flexibility. Here, we present a new conceptual framework, Ratio of Concordance Preference (RCP), that uses double-stranded methylation data to quantify the flexibility and stability of the system that gave rise to a given set of patterns. We find that differentiated mammalian cells operate with high DNA methylation stability, consistent with earlier reports. Stem cells in culture and in embryos, in contrast, operate with reduc...

在储存与传递表观遗传信息（epigenetic information）时，生物体需要在保留过往环境条件相关信息的需求，与响应当前及未来环境中所携带信息的能力之间达成平衡。此类信息中的一部分由DNA甲基化（DNA methylation）编码，其可在亲本链与子链之间以不同的保真度进行传递。较高的保真度可使单个DNA分子的两条链之间形成较强的模式匹配性，进而在多轮DNA复制过程中维持模式稳定性；而较低的保真度则会降低模式匹配程度，从而带来更强的灵活性。在此我们提出一种全新的概念框架——一致性偏好比率（Ratio of Concordance Preference，RCP），该框架可利用双链甲基化数据，对产生特定模式集合的系统的灵活性与稳定性进行量化。我们发现，分化后的哺乳动物细胞以较高的DNA甲基化稳定性运行，这与此前的研究报道相符。相比之下，体外培养与胚胎内的干细胞则以……（原文未完整给出）