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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Epigenetic control of gene expression: Potential implications for cancer treatment
Francesco Perri,Francesco Longo,Mario Giuliano,Mario Giuliano,Francesco Sabbatino,Gianfranco Favia,Franco Ionna,Raffaele Addeo,G Della Vittoria Scarpati,G. Di Lorenzo,Salvatore Pisconti +10 more
TL;DR: Drugs that inhibit DNA methylation or histone deacetylation have been studied for the reactivation of tumor suppressor genes and repression of cancer cell growth.
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Epigenetic Regulation of Mesenchymal Stem Cells: A Focus on Osteogenic and Adipogenic Differentiation
Chad M. Teven,Xing Liu,Xing Liu,Ning Hu,Ning Hu,Ni Tang,Ni Tang,Stephanie H. Kim,Enyi Huang,Enyi Huang,Ke Yang,Ke Yang,Mi Li,Mi Li,Jian-Li Gao,Jian-Li Gao,Hong Liu,Hong Liu,Ryan B. Natale,Gaurav Luther,Qing Luo,Qing Luo,Linyuan Wang,Richard Rames,Yang Bi,Yang Bi,Jinyong Luo,Jinyong Luo,Hue H. Luu,Rex C. Haydon,Russell R. Reid,Tong-Chuan He,Tong-Chuan He +32 more
TL;DR: The effect of epigenetic modifications on MSC multipotency and differentiation, with a focus on osteogenic and adipogenic differentiation is reviewed, including clinical applications of MSC epigenetics and nuclear reprogramming.
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Strategies for discovery and validation of methylated and hydroxymethylated DNA biomarkers.
TL;DR: The development of DNA methylation‐ and hydroxymethylation‐based biomarkers is an exciting and rapidly evolving area of research that holds promise for potential applications in diverse clinical settings.
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Epigenetic regulation in pluripotent stem cells: a key to breaking the epigenetic barrier.
TL;DR: This review covers the current understanding of the spatio-temporal regulation of epigenetics in pluripotent and differentiated cells, and discusses how cells determine their identity and overcome the epigenetic barrier during the reprogramming process.
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The role of epigenetics in genetic and environmental epidemiology.
TL;DR: The importance of including epigenetics in genetic and environmental epidemiology studies is described, a conceptual framework when considering epigenetic data in population-based studies is provided, and the many challenges that lie ahead are touched upon.
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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