Nature:DNA甲基化分布图

【字体: 时间:2008年09月28日 来源:Nature

  


DNA甲基化是表观遗传修饰的一个重要机制,它能从一个DNA序列产生不同模式的基因表达。它对正常发育至关重要,其功能失常可引起癌症和其他异常。现在,研究人员利用高通量亚硫酸氢盐测序与单分子测序相结合的方法,以核苷酸分辨率获得了在胚胎干细胞中和在由它们形成的各种不同的细胞类型中DNA甲基化的一个分布图。

该分布图显示了基因组中甲基化随细胞发育(如当胚胎干细胞成熟成为神经细胞时)而变化的特定点。更具普遍意义的是,这种方法对于与发育生物学、癌症和再生医学相关的细胞群的表观遗传分析将会是有价值的。

Nature 454, 766-770 (7 August 2008) | doi:10.1038/nature07107;

Genome-scale DNA methylation maps of pluripotent and differentiated cells

Alexander Meissner1,2,3,9, Tarjei S. Mikkelsen2,4,9, Hongcang Gu2, Marius Wernig1, Jacob Hanna1, Andrey Sivachenko2, Xiaolan Zhang2, Bradley E. Bernstein2,5,6, Chad Nusbaum2, David B. Jaffe2, Andreas Gnirke2, Rudolf Jaenisch1,7 & Eric S. Lander1,2,7,8

1 Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
2 Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
3 Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA
4 Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
5 Molecular Pathology Unit and Center for Cancer Research, MGH, Charlestown, Massachusetts 02129, USA
6 Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
7 Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
8 Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02114, USA
These authors contributed equally to this work.

婵犲痉鏉库偓妤佹叏閻戣棄纾绘繛鎴欏灪閸婅埖绻濋棃娑卞剰缂佺姷鍠栭弻銊╂偆閸屾稑顏� 细胞计数,看上海科进!

DNA methylation is essential for normal development1, 2, 3 and has been implicated in many pathologies including cancer4, 5. Our knowledge about the genome-wide distribution of DNA methylation, how it changes during cellular differentiation and how it relates to histone methylation and other chromatin modifications in mammals remains limited. Here we report the generation and analysis of genome-scale DNA methylation profiles at nucleotide resolution in mammalian cells. Using high-throughput reduced representation bisulphite sequencing6 and single-molecule-based sequencing, we generated DNA methylation maps covering most CpG islands, and a representative sampling of conserved non-coding elements, transposons and other genomic features, for mouse embryonic stem cells, embryonic-stem-cell-derived and primary neural cells, and eight other primary tissues. Several key findings emerge from the data. First, DNA methylation patterns are better correlated with histone methylation patterns than with the underlying genome sequence context. Second, methylation of CpGs are dynamic epigenetic marks that undergo extensive changes during cellular differentiation, particularly in regulatory regions outside of core promoters. Third, analysis of embryonic-stem-cell-derived and primary cells reveals that 'weak' CpG islands associated with a specific set of developmentally regulated genes undergo aberrant hypermethylation during extended proliferation in vitro, in a pattern reminiscent of that reported in some primary tumours. More generally, the results establish reduced representation bisulphite sequencing as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine.

 

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