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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Book ChapterDOI
Genome-wide epigenetic modifications in cancer
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TL;DR: A brief survey of recent experimental progress in DNA-based single-Molecule electronics with special focus on single-molecule conductance and I–V characteristics of individual DNA molecules is given.
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Polycomb protein SCML2 facilitates H3K27me3 to establish bivalent domains in the male germline
So Maezawa,Kazuteru Hasegawa,Kazuteru Hasegawa,Kazuteru Hasegawa,Masashi Yukawa,Masashi Yukawa,Naoki Kubo,Akihiko Sakashita,Akihiko Sakashita,Kris G. Alavattam,Kris G. Alavattam,Ho-Su Sin,Ho-Su Sin,Ho-Su Sin,Andrey V. Kartashov,Andrey V. Kartashov,Hiroyuki Sasaki,Artem Barski,Artem Barski,Satoshi H. Namekawa,Satoshi H. Namekawa +20 more
TL;DR: This study identifies a possible germline mechanism by which differentiated and unipotent germ cells give rise to a totipotent zygote following fertilization and proposes that SCML2-dependent H3K27me3 in the male germline prepares the expression of developmental regulator and somatic genes in embryonic development.
Journal ArticleDOI
Comparative methylomics reveals gene-body H3K36me3 in Drosophila predicts DNA methylation and CpG landscapes in other invertebrates
Lisa Nanty,Guillermo Carbajosa,Graham A. Heap,Francis Ratnieks,David A. van Heel,Thomas A. Down,Vardhman K. Rakyan +6 more
TL;DR: It is proposed that over evolutionary time, gene-body H3K36me3 has influenced gene- Body DNA methylation levels and, consequently, the gene- body CpG density bimodality characteristic of invertebrates that harbor CpGs methylation.
References
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