Data from: Proximal methylation features associated with nonrandom changes in gene body methylation

Background: Gene body methylation at CG dinucleotides is a widely conserved feature of methylated genomes but remains poorly understood. The Arabidopsis thaliana strain Cvi has depleted gene body methylation relative to the reference strain Col. Here, we leverage this natural epigenetic difference to investigate gene body methylation stability. Results: Recombinant inbred lines derived from Col and Cvi were used to examine the transmission of distinct gene body methylation states. The vast majority of genic CG methylation patterns are faithfully transmitted over nine generations according to parental genotype, with only 1–4% of CGs either losing or gaining methylation relative to the parent. Genic CGs that fail to maintain the parental methylation state are shared among independent lines, suggesting that these are not random occurrences. We use a logistic regression framework to identify features that best predict sites that fail to maintain parental methylation state. Intermediate levels of CG methylation around a dynamic CG site and high methylation variability across many A. thaliana strains at that site are the strongest predictors. These data suggest that the dynamic CGs we identify are not specific to the Col–Cvi recombinant inbred lines but have an epigenetic state that is inherently less stable within the A. thaliana species. Extending this, variably methylated genic CGs in maize and Brachypodium distachyon are also associated with intermediate local CG methylation. Conclusions: These results provide new insights into the features determining the inheritance of gene body methylation and demonstrate that two different methylation equilibria can be maintained within single individuals.

研究背景：CG二核苷酸（CG dinucleotides）处的基因体甲基化是甲基化基因组中广泛保守的特征，但其具体调控机制仍未被充分阐明。模式植物拟南芥（Arabidopsis thaliana）的Cvi品系相较于参考品系Col，其基因体甲基化水平存在显著缺失。本研究利用这一天然表观遗传差异，探究基因体甲基化的稳定性。
研究结果：本研究采用由Col和Cvi品系构建的重组自交系（recombinant inbred lines），分析不同基因体甲基化状态的传递规律。结果显示，绝大多数基因区域的CG甲基化模式可依据亲本基因型在连续九代中稳定传递，仅1%~4%的CG位点相较于亲本发生甲基化丢失或获得。无法维持亲本甲基化状态的基因区CG位点在多个独立株系中存在共享现象，表明此类事件并非随机发生。我们通过逻辑回归（logistic regression）框架，筛选出可最佳预测无法维持亲本甲基化状态位点的特征：动态CG位点周围CG甲基化水平处于中等程度，以及该位点在多种拟南芥品系中呈现高甲基化变异度，这两项为最强预测因子。上述数据表明，本研究鉴定的动态CG位点并非Col-Cvi重组自交系所特有，其表观遗传状态在拟南芥物种中本身就具有较低的稳定性。进一步延伸分析发现，玉米（maize）与二穗短柄草（Brachypodium distachyon）中存在可变甲基化的基因区CG位点，同样与局部中等水平CG甲基化相关。
研究结论：本研究结果为解析基因体甲基化的遗传决定特征提供了新的认知，并证实单个个体可同时维持两种不同的甲基化平衡状态。