Genome-scale DNA methylation oscillations in pluripotent cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA305881 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2993440_1.fastq.gz | Fastqsanger.gz | |||
| SRR2993440_2.fastq.gz | Fastqsanger.gz | |||
| SRR2993450_1.fastq.gz | Fastqsanger.gz | |||
| SRR2993450_2.fastq.gz | Fastqsanger.gz | |||
| SRR2993460_1.fastq.gz | Fastqsanger.gz |
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Project description:We report the generation and analysis of genome-scale DNA methylation profiles at nucleotide resolution in mammalian cells. Using high-throughput Reduced Representation Bisulfite Sequencing (RRBS) and single-molecule-based sequencing, we generated DNA methylation maps covering the vast majority of CpG islands, and a representative sampling of conserved non-coding elements, transposons and other genomic features, for murine embryonic stem (ES) cells, ES-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 ES-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 tumors. More generally, the results establish RRBS as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine. Keywords: High-throughput Reduced Representation Bisulfite Sequencing (RRBS), Illumina, cell type comparison Reduced representation bisulfite sequencing (MspI,~40-220bp size fraction) of 18 murine cell types. Raw sequence data files for this study are available for download from the SRA FTP site at ftp://ftp.ncbi.nlm.nih.gov/sra/Studies/SRP000/SRP000179
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Project description:We report the generation and analysis of genome-scale DNA methylation profiles at nucleotide resolution in mammalian cells. Using high-throughput Reduced Representation Bisulfite Sequencing (RRBS) and single-molecule-based sequencing, we generated DNA methylation maps covering the vast majority of CpG islands, and a representative sampling of conserved non-coding elements, transposons and other genomic features, for murine embryonic stem (ES) cells, ES-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 ES-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 tumors. More generally, the results establish RRBS as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine. Keywords: High-throughput Reduced Representation Bisulfite Sequencing (RRBS), Illumina, cell type comparison
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Project description:Mouse embryonic stem cells (ESCs) primed for differentiation display dynamic heterogeneity characterised by stochastic switching between transcriptional states, and recent advances have highlighted the heterogeneous and dynamic nature of DNA methylation in these. Using single cell sequencing we report global oscillations in ESC DNA methylation that affect particularly CpG poor regions including distal enhancers. These oscillations are dependent on DNA methylation turnover by Dnmt3 and Tet enzymes and influence the probability of transcriptional state switching. Our observations suggest that regulated DNA methylation heterogeneity may contribute to lineage priming in cells poised for differentiation.
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Project description: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.
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