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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Profiling DNA methylome landscapes of mammalian cells with single-cell reduced-representation bisulfite sequencing
TL;DR: A single-cell reduced-representation bisulfite sequencing technique in which the original RRBS method is modified by integrating all the experimental steps before PCR amplification into a single-tube reaction, which enables scRRBS to provide digitized methylation information on ∼1 million CpG sites within an individual diploid mouse or human cell at single-base resolution.
Journal ArticleDOI
Promoter DNA methylation couples genome-defence mechanisms to epigenetic reprogramming in the mouse germline
Jamie A. Hackett,Jamie A. Hackett,James P. Reddington,Colm E. Nestor,Colm E. Nestor,Donncha S. Dunican,Miguel R. Branco,Miguel R. Branco,Judith Reichmann,Wolf Reik,Wolf Reik,M. Azim Surani,Ian R. Adams,Richard R. Meehan,Richard R. Meehan +14 more
TL;DR: It is proposed that genes involved in genome defence are developmentally regulated primarily by promoter DNA methylation as a sensory mechanism that is coupled to the potential for TE activation during global 5mC erasure, thereby acting as a failsafe to ensure TE suppression and maintain genomic integrity in the germline.
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Evolution of the cancer genome
TL;DR: How cancer genomes are beginning to be investigated from an evolutionary perspective is outlined, recent progress in the cataloging of somatic genetic and genomic alterations is described, and the contributions of germline as well as epigenetic factors to cancer genome evolution are investigated.
Journal ArticleDOI
Gestational Choline Supply Regulates Methylation of Histone H3, Expression of Histone Methyltransferases G9a (Kmt1c) and Suv39h1 (Kmt1a), and DNA Methylation of Their Genes in Rat Fetal Liver and Brain
TL;DR: Data show that maternal choline supply during pregnancy modifies fetal histone and DNA methylation, suggesting that a concerted epigenomic mechanism contributes to the long term developmental effects of varied choline intake in utero.
Journal ArticleDOI
Short-Read Sequencing Technologies for Transcriptional Analyses
Stacey A. Simon,Jixian Zhai,Raja Sekhar Nandety,Kevin McCormick,Jia Zeng,Diego Mejia,Blake C. Meyers +6 more
TL;DR: The impact of these methods on plant biology is reviewed, which includes published studies from animal systems when the methods are broadly applicable, and the tremendous depth of sequencing facilitates de novo transcript discovery, which replaces traditional expressed sequence tag (EST) sequencing.
References
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A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells
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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
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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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