Human DNA methylomes at base resolution show widespread epigenomic differences Export

@article{citeulike:5942193, abstract = {DNA cytosine methylation is a central epigenetic modification that has essential roles in cellular processes including genome regulation, development and disease. Here we present the first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA–protein interaction for several key regulatory factors. Widespread differences were identified in the composition and patterning of cytosine methylation between the two genomes. Nearly one-quarter of all methylation identified in embryonic stem cells was in a non-CG context, suggesting that embryonic stem cells may use different methylation mechanisms to affect gene regulation. Methylation in non-CG contexts showed enrichment in gene bodies and depletion in protein binding sites and enhancers. Non-CG methylation disappeared upon induced differentiation of the embryonic stem cells, and was restored in induced pluripotent stem cells. We identified hundreds of differentially methylated regions proximal to genes involved in pluripotency and differentiation, and widespread reduced methylation levels in fibroblasts associated with lower transcriptional activity. These reference epigenomes provide a foundation for future studies exploring this key epigenetic modification in human disease and development.}, author = {Lister, Ryan and Pelizzola, Mattia and Dowen, Robert H. and Hawkins, R. David and Hon, Gary and Tonti-Filippini, Julian and Nery, Joseph R. and Lee, Leonard and Ye, Zhen and Ngo, Que-Minh and Edsall, Lee and Antosiewicz-Bourget, Jessica and Stewart, Ron and Ruotti, Victor and Millar, A. Harvey and Thomson, James A. and Ren, Bing and Ecker, Joseph R.}, booktitle = {Nature}, citeulike-article-id = {5942193}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature08514}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature08514}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19829295}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19829295}, day = {14}, doi = {10.1038/nature08514}, issn = {0028-0836}, journal = {Nature}, keywords = {dna-methylation, genome-wide, human}, month = {October}, number = {7271}, pages = {315--322}, posted-at = {2009-10-28 11:51:39}, priority = {2}, publisher = {Nature Publishing Group}, title = {Human DNA methylomes at base resolution show widespread epigenomic differences }, url = {http://dx.doi.org/10.1038/nature08514}, volume = {462}, year = {2009} }

TY - JOUR ID - citeulike:5942193 L3 - citeulike-article-id:5942193 N2 - DNA cytosine methylation is a central epigenetic modification that has essential roles in cellular processes including genome regulation, development and disease. Here we present the first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA–protein interaction for several key regulatory factors. Widespread differences were identified in the composition and patterning of cytosine methylation between the two genomes. Nearly one-quarter of all methylation identified in embryonic stem cells was in a non-CG context, suggesting that embryonic stem cells may use different methylation mechanisms to affect gene regulation. Methylation in non-CG contexts showed enrichment in gene bodies and depletion in protein binding sites and enhancers. Non-CG methylation disappeared upon induced differentiation of the embryonic stem cells, and was restored in induced pluripotent stem cells. We identified hundreds of differentially methylated regions proximal to genes involved in pluripotency and differentiation, and widespread reduced methylation levels in fibroblasts associated with lower transcriptional activity. These reference epigenomes provide a foundation for future studies exploring this key epigenetic modification in human disease and development. IS - 7271 JF - Nature SN - 0028-0836 EP - 322 TI - Human DNA methylomes at base resolution show widespread epigenomic differences PB - Nature Publishing Group VL - 462 T2 - Nature SP - 315 KW - dna-methylation KW - genome-wide KW - human AU - Lister, Ryan AU - Pelizzola, Mattia AU - Dowen, Robert AU - Hawkins, David AU - Hon, Gary AU - Tonti-Filippini, Julian AU - Nery, Joseph AU - Lee, Leonard AU - Ye, Zhen AU - Ngo, Que-Minh AU - Edsall, Lee AU - Antosiewicz-Bourget, Jessica AU - Stewart, Ron AU - Ruotti, Victor AU - Millar, Harvey AU - Thomson, James AU - Ren, Bing AU - Ecker, Joseph PY - 2009/10/14/ UR - http://dx.doi.org/10.1038/nature08514 ER -