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A population-epigenetic model to infer site-specific methylation rates from double-stranded DNA methylation patterns

机译：从双链DNA甲基化模式推断位点特异性甲基化率的种群表观遗传模型

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Cytosine methylation is an epigenetic mechanism in eukaryotes that is often associated with stable transcriptional silencing, such as in X-chromosome inactivation and genomic imprinting. Aberrant methylation patterns occur in several inherited human diseases and in many cancers. To understand how methylated and unmethylated states of cytosine residues are transmitted during DNA replication, we develop a population-epigenetic model of DNA methylation dynamics. The model is informed by our observation that de novo methylation can occur on the daughter strand while leaving the opposing cytosine unmethylated, as revealed by the patterns of methylation on the two complementary strands of individual DNA molecules. Under our model, we can infer sitespecific rates of both maintenance and de novo methylation, values that determine the fidelity of methylation inheritance, from double-stranded methylation data. This approach can be used for populations of cells obtained from individuals without the need for cell culture. We use our method to infer cytosine methylation rates at several sites within the promoter of the human gene FMR1.
机译：胞嘧啶甲基化是真核生物中的表观遗传机制，通常与稳定的转录沉默相关，例如在X染色体失活和基因组印迹中。异常的甲基化模式发生在几种遗传的人类疾病和许多癌症中。若要了解如何在DNA复制过程中传递胞嘧啶残基的甲基化和未甲基化状态，我们建立了DNA甲基化动力学的群体表观遗传模型。该模型是根据我们的观察结果告知的，从头甲基链可发生从头甲基化，而相反的胞嘧啶则未甲基化，这可通过单个DNA分子两条互补链上的甲基化模式来揭示。在我们的模型下，我们可以根据双链甲基化数据推断维持和重新甲基化的位点特异性速率，这些值决定了甲基化遗传的保真度。该方法可用于从个体获得的细胞群体，而无需细胞培养。我们使用我们的方法来推断人类基因FMR1启动子中多个位点的胞嘧啶甲基化率。

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