DNA methylation of enhancers is dynamic, cell-type specific, and vital for cell fate progression. However, current models inadequately define its role within the hierarchy of gene regulation. Analysis of independent datasets shows an unanticipated overlap between DNA methylation and chromatin accessibility at enhancers of steady-state stem cells, suggesting that these two opposing features might exist concurrently. To define their temporal relationship, we developed ATAC-Me, which probes accessibility and methylation from single DNA library preparations. We identified waves of accessibility occurring rapidly across thousands of myeloid enhancers in a monocyte-to-macrophage cell fate model. Prolonged methylation states were observed at a majority of these sites, while transcription of nearby genes tracked closely with accessibility. ATAC-Me uncovers a significant disconnect between chromatin accessibility, DNA methylation status, and gene activity. This unexpected observation highlights the value of ATAC-Me in constructing precise molecular timelines for understanding the role of DNA methylation in gene regulation.

中文翻译：

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ATAC-Me在细胞命运转变过程中捕获了动态染色质可及性基因座的延长的DNA甲基化。

增强子的DNA甲基化是动态的，细胞类型特异性的，对细胞命运的发展至关重要。但是，当前的模型不足以在基因调控的层次结构中定义其作用。对独立数据集的分析显示，稳态干细胞增强子的DNA甲基化和染色质可及性之间存在意想不到的重叠，表明这两个相对的特征可能同时存在。为了定义它们的时间关系，我们开发了ATAC-Me，它可以从单个DNA文库制备物中探查可及性和甲基化。我们确定了单核细胞到巨噬细胞命运模型中成千上万的髓样增强子之间迅速发生的可及性波。在大多数这些位点观察到延长的甲基化状态，而附近基因的转录与可及性密切相关。ATAC-Me发现了染色质可访问性，DNA甲基化状态和基因活性之间的重大脱节。这一出乎意料的发现凸显了ATAC-Me在构建精确的分子时间表以了解DNA甲基化在基因调控中的作用的价值。