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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DNA methylation reprogramming in cancer: does it act by re-configuring the binding landscape of Polycomb repressive complexes?
TL;DR: It is speculated that cancer‐associated reprogramming of the DNA methylome leads to an altered Polycomb binding landscape, influencing gene expression by multiple modes, and could directly drive carcinogenesis and disease progression.
Journal ArticleDOI
Mapping Allele-Specific DNA Methylation: A New Tool for Maximizing Information from GWAS
TL;DR: The landscape of allele-specific DNA methylation (ASM) in the human genome shows the widespread occurrence of this phenomenon among human genes and its basic implications for gene regulation and genetic-epigenetic interactions are discussed.
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Genome wide analysis of DNA methylation and gene expression changes in the mouse lung following subchronic arsenate exposure
Frank Boellmann,Lu Zhang,Harvey J. Clewell,Gary P. Schroth,Elaina M. Kenyon,Melvin E. Andersen,Russell S. Thomas +6 more
TL;DR: The results suggest that differential methylation following As treatment may only play a permissive role in regulating expression, and the subset of 17 genes that showed an inverse relationship between As-related methylation and expression included a substantial number that has been demonstrated to play a functional role in cancer-related processes.
Journal ArticleDOI
Mapping of Variable DNA Methylation Across Multiple Cell Types Defines a Dynamic Regulatory Landscape of the Human Genome
Junchen Gu,Michael Stevens,Xiaoyun Xing,Daofeng Li,Bo Zhang,Jacqueline E. Payton,Eugene M. Oltz,James N. Jarvis,Kaiyu Jiang,Theodore J. Cicero,Joseph F. Costello,Ting Wang +11 more
TL;DR: An in-depth analysis of 54 single-CpG-resolution DNA methylomes of normal human cell types by integrating high-throughput sequencing-based methylation data found that VMRs enrich for histone modifications indicative of enhancers, suggesting their role as regulatory elements marking cell type specificity.
Journal ArticleDOI
Canfam_GSD: De novo chromosome-length genome assembly of the German Shepherd Dog (Canis lupus familiaris) using a combination of long reads, optical mapping, and Hi-C.
Matthew A. Field,Matthew A. Field,Benjamin D. Rosen,Olga Dudchenko,Olga Dudchenko,Eva K. F. Chan,Eva K. F. Chan,Andre E. Minoche,Andre E. Minoche,Richard Edwards,Kirston Barton,Kirston Barton,Ruth J. Lyons,Daniel Enosi Tuipulotu,Vanessa M. Hayes,Vanessa M. Hayes,Vanessa M. Hayes,Arina D. Omer,Arina D. Omer,Zane Colaric,Zane Colaric,Jens Keilwagen,Ksenia Skvortsova,Ozren Bogdanovic,Ozren Bogdanovic,Martin A. Smith,Martin A. Smith,Erez Lieberman Aiden,Timothy P. L. Smith,Robert A. Zammit,J. William O. Ballard +30 more
TL;DR: GSD genome assembly and annotation were produced with major improvement in completeness, continuity, and quality over the existing canid reference, enabling further research related to canine diseases, the evolutionary relationships of canids, and other aspects of canid biology.
References
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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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