Genome-scale DNA methylation maps of pluripotent and differentiated cells
Alexander Meissner,Tarjei S. Mikkelsen,Tarjei S. Mikkelsen,Hongcang Gu,Marius Wernig,Jacob H. Hanna,Andrey Sivachenko,Xiaolan Zhang,Bradley E. Bernstein,Bradley E. Bernstein,Chad Nusbaum,David B. Jaffe,Andreas Gnirke,Rudolf Jaenisch,Eric S. Lander +14 more
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TLDR
Low-throughput reduced representation bisulphite sequencing is established as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine.Abstract:
DNA methylation is essential for normal development and has been implicated in many pathologies including cancer. 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 sequencing 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.read more
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Estimation of blood cellular heterogeneity in newborns and children for epigenome-wide association studies.
TL;DR: The findings suggest that the minfi method may provide suitable estimates of white blood cell composition for samples from adults and older children, but may not currently be appropriate for EWAS involving newborns or young children.
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The role of DNA methylation in mammalian development
TL;DR: A clearer picture of the dynamic patterns of DNA methylation throughout gametogenesis, preimplantation development and early lineage commitment is beginning to emerge and the continuing use of next-generation technologies to elucidate genome-wide methylation patterns in a variety of cellular contexts will further understanding of how this epigenetic mark contributes to lineage commitment, differentiation and pluripotency and, ultimately, to human health and disease.
Journal ArticleDOI
Developmentally Programmed 3′ CpG Island Methylation Confers Tissue- and Cell-Type-Specific Transcriptional Activation
Da-Hai Yu,Carol B. Ware,Robert A. Waterland,Jiexin Zhang,Miao-Hsueh Chen,Manasi Gadkari,Govindarajan Kunde-Ramamoorthy,Lagina M. Nosavanh,Lanlan Shen +8 more
TL;DR: It is confirmed that developmentally programmed 3′ CGI methylation confers tissue- and cell-type-specific gene activation in vivo and luciferase reporter assays provided evidence that 3′cgi methylation regulates transcriptional activation via a CTCF-dependent enhancer-blocking mechanism.
Journal ArticleDOI
Notch signaling genes: Myogenic DNA hypomethylation and 5-hydroxymethylcytosine
Jolyon Terragni,Guoqiang Zhang,Zhiyi Sun,Sriharsa Pradhan,Lingyun Song,Gregory E. Crawford,Michelle Lacey,Melanie Ehrlich +7 more
TL;DR: Epigenetics studies and gene expression profiles suggest that hypomethylation and/or hydroxymethylation help control expression of Notch signaling genes in heart, brain, myoblasts, myotubes, and within skeletal muscle myofibers.
Journal ArticleDOI
A complex association between DNA methylation and gene expression in human placenta at first and third trimesters
Yen Ching Lim,Jie Li,Yiyun Ni,Qi Liang,Junjiao Zhang,George S. H. Yeo,Jianxin Lyu,Shengnan Jin,Chunming Ding +8 more
TL;DR: A wide range of DNA methylation and gene expression changes were observed at different gestational ages, indicating that epigenetic regulation of placenta development is more complex than previously envisioned.
References
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A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells
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Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
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TL;DR: Insight is given into the connections between chromatin modifications and transcriptional regulatory activity and a novel functional enhancer for the carnitine transporter SLC22A5 (OCTN2) is uncovered, providing a new tool for the functional annotation of the human genome.
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