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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Genomic landscape of human allele-specific DNA methylation
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Genomic landscape of human allele-specific DNA methylation

机译：人类等位基因特异性DNA甲基化的基因组景观

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摘要

DNA methylation mediates imprinted gene expression by passing an epigenomic state across generations and differentially marking specific regulatory regions' on maternal and paternal alleles. Imprinting has been tied to the evolution of the placenta in mammals and defects of imprinting have been associated with human diseases. Although recent advances in genome sequencing have revolutionized the study of DNA methylation, existing methylome data remain largely untapped in the study of imprinting. We present a statistical model to describe allele-specific methylation (ASM) in data from high-throughput short-read bisulfite sequencing. Simulation results indicate technical specifications of existing methylome data, such as read length and coverage, are sufficient for full-genome ASM profiling based on our model. We used our model to analyze methylomes for a diverse set of human cell types, including cultured and uncultured differentiated cells, embryonic stem cells and induced pluripotent stem cells. Regions of ASM identified most consistently across methylomes are tightly connected with known imprinted genes and precisely delineate the boundaries of several known imprinting control regions. Predicted regions of ASM common to multiple cell types frequently mark noncoding RNA promoters and represent promising starting points for targeted validation. More generally, our model provides the analytical complement to cutting-edge experimental technologies for surveying ASM in specific cell types and across species.
机译：DNA甲基化通过跨越几代人的表观基因组状态并在母本和父本等位基因上差异标记特定的调控区域来介导印记的基因表达。印迹与哺乳动物胎盘的进化有关，并且印迹的缺陷与人类疾病有关。尽管基因组测序的最新进展彻底改变了DNA甲基化的研究，但现有的甲基化组数据在印迹研究中仍未开发。我们提出了一种统计模型，用于描述高通量短读亚硫酸氢盐测序数据中的等位基因特异性甲基化（ASM）。仿真结果表明，基于我们的模型，现有的甲基化组数据的技术规格，例如读取长度和覆盖范围，足以用于全基因组ASM分析。我们使用我们的模型分析了多种人类细胞类型的甲基化组，包括培养和未培养的分化细胞，胚胎干细胞和诱导性多能干细胞。在甲基化组中最一致地鉴定出的ASM区域与已知的印迹基因紧密相连，并精确地描绘了几个已知的印迹控制区域的边界。多种细胞类型共有的ASM预测区域经常标记非编码RNA启动子，并代表有针对性的有希望的起点。更笼统地说，我们的模型为用于调查特定细胞类型和跨物种的ASM的尖端实验技术提供了分析补充。

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    Fang Fang; Emily Hodges; Antoine Molaro; Matthew Dean; Gregory J. Harmon; Andrew D. Smith;

  • 作者单位

    Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, California;

    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724;

    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724;

    Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, California;

    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724;

    Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, California;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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