A population-epigenetic model to infer site-specific methylation rates from double-stranded DNA methylation patterns
A population-epigenetic model to infer site-specific methylation rates from double-stranded DNA methylation patterns
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DOI：
10.1073/pnas.0502036102
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发表时间：
2005-04-19
影响因子：
11.1
通讯作者：
Laird, CD
中科院分区：
文献类型：
--
作者：
Genereux, DP;Miner, BE;Laird, CD
胞嘧啶甲基化是真核生物中的一种表观遗传机制，通常与稳定的转录沉默有关，如X染色体失活和基因组印迹。异常甲基化模式出现在几种遗传性人类疾病和许多癌症中。为了了解DNA复制过程中胞嘧啶残基的甲基化和非甲基化状态是如何传递的，我们建立了DNA甲基化动力学的群体表观遗传模型。该模型是由我们的观察得到的，如单个DNA分子的两条互补链上的甲基化模式所揭示的那样，子链上可以发生从头甲基化，而对面的胞嘧啶则没有甲基化。在我们的模型下，我们可以从双链甲基化数据中推断出维持甲基化和从头甲基化的位点特异性比率，这两个值决定了甲基化遗传的保真度。这种方法可以用于从个体获得的细胞群体，而不需要细胞培养。我们使用我们的方法来推断人类基因FMR1启动子内几个位置的胞嘧啶甲基化速率。
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 site-specific 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.