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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Vitamin D and the epigenome
TL;DR: Regulation of the vitamin D system by epigenetic modifications and how vitamin D contributes to the maintenance of the epigenome is discussed, and its impact in health and disease is evaluated.
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High-throughput bisulfite sequencing in mammalian genomes.
Zachary D. Smith,Hongcang Gu,Christoph Bock,Christoph Bock,Andreas Gnirke,Alexander Meissner,Alexander Meissner +6 more
TL;DR: An extensive, optimized protocol for generating RRBS libraries is provided and the power of this strategy for methylome profiling is discussed, which includes information on sequence analysis and the relative coverage over genomic regions of interest for a representative mouse MspI generated RRBS library.
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The molecular bases of the suicidal brain
TL;DR: The key molecular changes that are associated with suicidality are explored and some promising avenues for future research are discussed.
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An evaluation of analysis pipelines for DNA methylation profiling using the Illumina HumanMethylation450 BeadChip platform.
Francesco Marabita,Malin Almgren,Malene E. Lindholm,Sabrina Ruhrmann,Fredrik Fagerström-Billai,Maja Jagodic,Carl Johan Sundberg,Tomas J. Ekström,Andrew E. Teschendorff,Jesper Tegnér,David Gomez-Cabrero +10 more
TL;DR: A comparative analysis using a comprehensive data set suggests an efficient pipeline for proper identification of differentially methylated CpGs using the Illumina 450K arrays.
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CpG methylation of half-CRE sequences creates C/EBPα binding sites that activate some tissue-specific genes
Vikas Rishi,Paramita Bhattacharya,Raghunath Chatterjee,Julian M. Rozenberg,Jianfei Zhao,Kimberly Glass,Peter C. FitzGerald,Charles Vinson +7 more
TL;DR: It is shown that CpG methylation of the CRE sequence (TGACGTCA) enhances the DNA binding of the C/EBPα transcription factor, a protein critical for activation of differentiation in various cell types.
References
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A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells
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