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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Chromatin Signatures in Multipotent Human Hematopoietic Stem Cells Indicate the Fate of Bivalent Genes during Differentiation
Kairong Cui,Chongzhi Zang,Tae-Young Roh,Dustin E. Schones,Richard W. Childs,Weiqun Peng,Keji Zhao +6 more
TL;DR: The data suggest that gene expression changes during differentiation are programmed by chromatin modifications present at the HSC/HPC stage and provide a resource for enhancer and promoter identification.
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Next-generation genomics: an integrative approach.
TL;DR: This Review discusses emerging issues and strategies related to data integration in the era of next-generation genomics.
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Dynamic CpG island methylation landscape in oocytes and preimplantation embryos
Sébastien A. Smallwood,Shin-ichi Tomizawa,Felix Krueger,Nico Ruf,Natasha Carli,Anne Segonds-Pichon,Shun Sato,Kenichiro Hata,Simon Andrews,Gavin Kelsey,Gavin Kelsey +10 more
TL;DR: It is shown that CGI methylation in gametes is not entirely related to genomic imprinting but is a strong factor in determining methylation status in preimplantation embryos, suggesting a need to reassess mechanisms of post-fertilization demethylation.
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DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos
TL;DR: Recent technological advances in genome-wide DNA methylation analysis and the functional description of novel enzymatic DNA demethylation pathways have provided significant insights into the molecular processes that prepare the mammalian embryo for normal development.
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Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers
TL;DR: Analysis of comprehensive mapping of transcription start sites in human lymphoblastoid B cell and chronic myelogenous leukemic ENCODE Tier 1 cell lines identifies a common architecture of initiation, including tightly spaced (110 bp apart) divergent initiation, similar frequencies of core promoter sequence elements, highly positioned flanking nucleosomes and two modes of transcription factor binding.
References
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A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells
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