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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Journal ArticleDOI
Mechanisms of DNA methylation and demethylation in mammals
Ghislain Auclair,Michael Weber +1 more
TL;DR: The importance of DNA methylation for genome regulation and the mechanisms that remodel the DNA methylome during mammalian development are discussed, in particular the involvement of the rediscovered modified base 5-hydroxymethylcytosine.
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Allele-specific DNA methylation: beyond imprinting
TL;DR: ASM, ASE and ASTF have now been mapped genome-wide by microarray-based methods and NextGen sequencing, and the precise mechanisms by which this occurs are not yet understood, but there are some testable hypotheses and already a few direct clues.
Journal ArticleDOI
Pioneer factors: directing transcriptional regulators within the chromatin environment
TL;DR: Evidence of an interplay between pioneer factors and the epigenome that could be central to this process of recruitment of downstream transcription factors to establish lineage-specific transcriptional programs is presented.
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Derepression of Polycomb targets during pancreatic organogenesis allows insulin-producing beta-cells to adopt a neural gene activity program.
Joris van Arensbergen,Javier García-Hurtado,Ignasi Moran,Miguel A. Maestro,Xiaobo Xu,Mark Van de Casteele,Anouchka L. Skoudy,Matteo Palassini,Harry Heimberg,Jorge Ferrer +9 more
TL;DR: It is reported that despite their endodermal origin, beta-cells show a transcriptional and active chromatin signature that is most similar to ectoderm-derived neural tissues, revealing a dynamic regulation of Polycomb repression programs that shape the identity of differentiated Beta-cells.
Journal ArticleDOI
Dnmt3L Antagonizes DNA Methylation at Bivalent Promoters and Favors DNA Methylation at Gene Bodies in ESCs
Francesco Neri,Anna Krepelova,Danny Incarnato,Mara Maldotti,Caterina Parlato,Federico Galvagni,Filomena Matarese,Hendrik G. Stunnenberg,Salvatore Oliviero +8 more
TL;DR: In ESCs, Dnmt3L counteracts the activity of de novo DNA methylases to maintain hypomethylation at promoters of bivalent developmental genes.
References
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A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells
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