Genome-scale DNA methylation maps of pluripotent and differentiated cells Export

@article{citeulike:2970738, abstract = {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.}, author = {Meissner, Alexander and Mikkelsen, Tarjei S. and Gu, Hongcang and Wernig, Marius and Hanna, Jacob and Sivachenko, Andrey and Zhang, Xiaolan and Bernstein, Bradley E. and Nusbaum, Chad and Jaffe, David B. and Gnirke, Andreas and Jaenisch, Rudolf and Lander, Eric S.}, citeulike-article-id = {2970738}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature07107}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature07107}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18600261}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18600261}, day = {06}, doi = {10.1038/nature07107}, issn = {0028-0836}, journal = {Nature}, keywords = {analysis, dna-methylation, genome-wide, histones}, month = {July}, number = {7205}, pages = {766--770}, posted-at = {2009-11-06 11:01:13}, priority = {2}, publisher = {Nature Publishing Group}, title = {Genome-scale DNA methylation maps of pluripotent and differentiated cells}, url = {http://dx.doi.org/10.1038/nature07107}, volume = {454}, year = {2008} }

TY - JOUR ID - citeulike:2970738 L3 - citeulike-article-id:2970738 N2 - 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. IS - 7205 JF - Nature SN - 0028-0836 EP - 770 TI - Genome-scale DNA methylation maps of pluripotent and differentiated cells PB - Nature Publishing Group VL - 454 SP - 766 KW - analysis KW - dna-methylation KW - genome-wide KW - histones AU - Meissner, Alexander AU - Mikkelsen, Tarjei AU - Gu, Hongcang AU - Wernig, Marius AU - Hanna, Jacob AU - Sivachenko, Andrey AU - Zhang, Xiaolan AU - Bernstein, Bradley AU - Nusbaum, Chad AU - Jaffe, David AU - Gnirke, Andreas AU - Jaenisch, Rudolf AU - Lander, Eric PY - 2008/07/06/ UR - http://dx.doi.org/10.1038/nature07107 ER -