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
Citations
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Genome-wide age-related DNA methylation changes in blood and other tissues relate to histone modification, expression and cancer.
Zongli Xu,Jack A. Taylor +1 more
TL;DR: It is suggested that as cells acquire methylation at age-related sites, they have a lower threshold for malignant transformation that may explain in part the increase in cancer incidence with age.
Journal ArticleDOI
Massive transcriptional start site analysis of human genes in hypoxia cells
Katsuya Tsuchihara,Yutaka Suzuki,Hiroyuki Wakaguri,Takuma Irie,Kousuke Tanimoto,Shin-ichi Hashimoto,Kouji Matsushima,Junko Mizushima-Sugano,Riu Yamashita,Kenta Nakai,David Bentley,Hiroyasu Esumi,Sumio Sugano +12 more
TL;DR: The novel dynamic figure of thehuman gene transcriptome will deepen the understanding of the transcriptional program of the human genome as well as bringing new insights into the biology of cancer cells in hypoxia.
Journal ArticleDOI
Genome-wide prediction of transcription factor binding sites using an integrated model.
TL;DR: Chromia significantly outperforms other methods in the identification of 13 transcription factor binding sites in mouse embryonic stem cells, evaluated by both binding (ChIP-seq) and functional (RNA interference knockdown) experiments.
Journal ArticleDOI
Analysis of epigenetic changes in survivors of preterm birth reveals the effect of gestational age and evidence for a long term legacy
Mark N. Cruickshank,Mark N. Cruickshank,Alicia Oshlack,Christiane Theda,Christiane Theda,Peter G Davis,Peter G Davis,David Martino,Penelope M. Sheehan,Yun Dai,Richard Saffery,Lex W. Doyle,Lex W. Doyle,Jeffrey M. Craig +13 more
TL;DR: Evidence is presented for widespread methylation differences between extreme preterm and term infants at birth that are largely resolved by 18 years of age, consistent with methylation changes associated with blood cell development, cellular composition, immune induction and age at these time points.
Journal ArticleDOI
Aberrant DNA methylation in contrast with mutations.
Toshikazu Ushijima,Kiyoshi Asada +1 more
TL;DR: Methylation is potentially reversible, unlike mutations, and these characteristics of methylation are opening up new fields of application and research.
References
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A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem 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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