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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Analysis of DNA Methylation in a Three-Generation Family Reveals Widespread Genetic Influence on Epigenetic Regulation
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Genetic and environmental influences interact with age and sex in shaping the human methylome
Jenny van Dongen,Michel G. Nivard,Gonneke Willemsen,Jouke-Jan Hottenga,Quinta Helmer,Conor V. Dolan,Erik A. Ehli,Gareth E. Davies,Maarten van Iterson,Charles E. Breeze,Stephan Beck,H. Eka D. Suchiman,Rick Jansen,Joyce B. J. van Meurs,Bastiaan T. Heijmans,P. Eline Slagboom,Dorret I. Boomsma +16 more
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References
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Journal ArticleDOI
DNA methylation patterns and epigenetic memory
TL;DR: The heritability of methylation states and the secondary nature of the decision to invite or exclude methylation support the idea that DNA methylation is adapted for a specific cellular memory function in development.
Journal ArticleDOI
A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells
Bradley E. Bernstein,Tarjei S. Mikkelsen,Tarjei S. Mikkelsen,Xiaohui Xie,Michael Kamal,Dana J. Huebert,James Cuff,Ben Fry,Alexander Meissner,Marius Wernig,Kathrin Plath,Rudolf Jaenisch,Alexandre Wagschal,Robert Feil,Stuart L. Schreiber,Stuart L. Schreiber,Eric S. Lander,Eric S. Lander +17 more
TL;DR: It is proposed that bivalent domains silence developmental genes in ES cells while keeping them poised for activation, highlighting the importance of DNA sequence in defining the initial epigenetic landscape and suggesting a novel chromatin-based mechanism for maintaining pluripotency.
Journal ArticleDOI
The epigenomics of cancer.
Peter A. Jones,Stephen B. Baylin +1 more
TL;DR: Recent advances in understanding how epigenetic alterations participate in the earliest stages of neoplasia, including stem/precursor cell contributions, are reviewed and the growing implications of these advances for strategies to control cancer are discussed.
Journal ArticleDOI
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Tarjei S. Mikkelsen,Manching Ku,Manching Ku,David B. Jaffe,Biju Issac,Biju Issac,Erez Lieberman Aiden,Erez Lieberman Aiden,Georgia Giannoukos,Pablo Alvarez,William Brockman,Tae Kyung Kim,Richard Koche,Richard Koche,Richard Koche,William Lee,Eric M. Mendenhall,Eric M. Mendenhall,Aisling O'Donovan,Aviva Presser,Carsten Russ,Xiaohui Xie,Alexander Meissner,Marius Wernig,Rudolf Jaenisch,Chad Nusbaum,Eric S. Lander,Eric S. Lander,Bradley E. Bernstein,Bradley E. Bernstein +29 more
TL;DR: The application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells is reported and it is shown that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms.
Journal ArticleDOI
Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome.
Nathaniel D. Heintzman,Rhona K. Stuart,Gary C. Hon,Yutao Fu,Christina W. Ching,R. David Hawkins,Leah O. Barrera,Sara Van Calcar,Chunxu Qu,Keith A. Ching,Wei Wang,Zhiping Weng,Roland Green,Gregory E. Crawford,Bing Ren +14 more
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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