DNA甲基化是表觀遺傳修飾的一個重要機制,，它能從一個DNA序列產(chǎn)生不同模式的基因表達,。它對正常發(fā)育至關(guān)重要，其功能失?？梢鸢┌Y和其他異?！，F(xiàn)在,，研究人員利用高通量亞硫酸氫鹽測序與單分子測序相結(jié)合的方法,，以核苷酸分辨率獲得了在胚胎干細胞中和在由它們形成的各種不同的細胞類型中DNA甲基化的一個分布圖。
該分布圖顯示了基因組中甲基化隨細胞發(fā)育（如當胚胎干細胞成熟成為神經(jīng)細胞時）而變化的特定點,。更具普遍意義的是,，這種方法對于與發(fā)育生物學,、癌癥和再生醫(yī)學相關(guān)的細胞群的表觀遺傳分析將會是有價值的。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
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.
