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
Long non-coding RNA PARTICLE bridges histone and DNA methylation
Valerie B. O'Leary,Sarah Hain,Doris Maugg,Jan Smida,Omid Azimzadeh,Soile Tapio,Saak V. Ovsepian,Michael J. Atkinson +7 more
TL;DR: Acting as a regulatory docking platform, the long non-coding RNA PARTICLE serves to interlink epigenetic modification machineries and represents a compelling innovative component necessary for gene silencing on a global scale.
Journal ArticleDOI
Differential gene body methylation and reduced expression of cell adhesion and neurotransmitter receptor genes in adverse maternal environment
J.-e. Oh,Nyasha Chambwe,S. Klein,Gal J,Andrews S,Georgia Gleason,Rita Shaknovich,Ari Melnick,Fabien Campagne,Miklós Tóth +9 more
TL;DR: Genome-wide DNA methylation analyses identified 2.3% of CpGs as differentially methylated by the adverse environment in ventral-hippocampal granule cells, neurons that can be linked to the anxiety phenotype, and clusters of DMSs were typically clustered and these clusters were preferentially located at gene bodies.
Journal ArticleDOI
Dynamic regulation of DNA methylation during mammalian development.
TL;DR: The distribution and function of DNA methylation in mammalian genomes is discussed, with particular emphasis on the waves of globalDNA methylation reprogramming occurring in early embryos and primordial germ cells.
Journal ArticleDOI
DNA Methyltransferase inhibition reverses epigenetically embedded phenotypes in lung cancer preferentially affecting Polycomb target genes
Antje Hascher,Ann-Kristin Haase,Katja Hebestreit,Christian Rohde,Hans-Ulrich Klein,Maria Rius,Dominik Jungen,Anika Witten,Monika Stoll,Isabell Schulze,Seishi Ogawa,Rainer Wiewrodt,Lara Tickenbrock,Wolfgang E. Berdel,Martin Dugas,Nils H. Thoennissen,Carsten Müller-Tidow +16 more
TL;DR: It is shown that metastatic capability of NSCLC is closely associated with DNA methylome alterations, and epigenetic modulation seems to be a potential therapeutic approach to prevent metastasis formation.
Journal ArticleDOI
Differential expression and DNA methylation of angiotensin type 1A receptors in vascular tissues during genetic hypertension development
TL;DR: The results suggest that the heightened AT1aR expression in SHRs is related to the AT2aR promoter hypo-methylation, which might be a consequence of the increased blood pressure and may be important in the maintenance of high blood pressure.
References
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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
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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
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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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