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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Oxidized C5-methyl cytosine bases in DNA: 5-Hydroxymethylcytosine; 5-formylcytosine; and 5-carboxycytosine.
Arne Klungland,Adam B. Robertson +1 more
TL;DR: An overview of the biochemistry and biology of 5-methylcytosine oxidation products is provided, suggesting that the Tet enzyme family is involved in an active DNA demethylation pathway.
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EpiGRAPH: user-friendly software for statistical analysis and prediction of (epi)genomic data
TL;DR: EpiGRAPH's practical utility is demonstrated in a case study on monoallelic gene expression and its novel approach to reproducible bioinformatic analysis is described.
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Epigenetic regulation of satellite cell activation during muscle regeneration
TL;DR: Evidence is presented suggesting an essential role for the antagonistic Polycomb group and Trithorax group proteins in the epigenetic marking of muscle-specific genes to ensure proper temporal and spatial expression during muscle regeneration.
Journal ArticleDOI
Comparison and quantitative verification of mapping algorithms for whole-genome bisulfite sequencing
Govindarajan Kunde-Ramamoorthy,Cristian Coarfa,Eleonora Laritsky,Noah J. Kessler,R. Alan Harris,Mingchu Xu,Rui Chen,Lanlan Shen,Aleksandar Milosavljevic,Robert A. Waterland +9 more
TL;DR: Of these algorithms, Bismark provides an attractive combination of processing speed, genomic coverage and quantitative accuracy, whereas Pash offers considerably higher genomic coverage.
Journal ArticleDOI
Epigenetics: DNA demethylation promotes skeletal myotube maturation
Marlinda Hupkes,Malin K.B. Jonsson,Wim J.J.M. Scheenen,Walter van Rotterdam,Ana M. Sotoca,Eugene P. van Someren,Marcel A.G. van der Heyden,Toon A.B. van Veen,Roselinde I. van Ravestein-van Os,S. Bauerschmidt,Ester Piek,Dirk L. Ypey,Everardus J.J. van Zoelen,Koen J. Dechering +13 more
TL;DR: Treatment of murine C2C12 mesenchymal progenitor cells with 10 μM of the DNA methylation inhibitor 5‐azacytidine (5AC) promotes myogenesis, resulting in myotubes with enhanced maturity as compared to untreated myot tubes, suggesting that genomic demethylation induced by 5AC overcomes an epigenetic barrier that prevents untreated C2 C12 myotube maturation.
References
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A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells
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