Project description:DNA methylation plays an important role in development and disease. The primary sites of DNA methylation in vertebrates are cytosines in the CpG dinucleotide context, which account for roughly three quarters of the total DNA methylation content in human and mouse cells. While the genomic distribution, inter-individual stability and functional role of CpG methylation are reasonably well understood, little is known about DNA methylation targeting CpA, CpC and CpT dinucleotides. Here we report a comprehensive analysis of non-CG methylation in 72 genome-scale DNA methylation maps across human pluripotent and differentiated cell types. We confirm non-CG methylation to be predominant in pluripotent cell types and observe an expected decrease upon differentiation and near complete absence in various differentiated cells. Our data highlight that non-CG methylation is highly variable and shows little conservation between different pluripotent cell lines. While we show a strong correlation of non-CG methylation and DNMT3 expression levels we find a statistical independence of non-CG methylation from pluripotency associated gene expression. Finally, non-CG methylation appears to be spatially correlated with CpG methylation. In summary these results contribute further to our understanding of DNA methylation in human cells and help clarify previous observations using a large representative sample set. Examination of nonCG DNA methylation patterns in pluripotent and differentiated cells
Project description:DNA methylation plays an important role in development and disease. The primary sites of DNA methylation in vertebrates are cytosines in the CpG dinucleotide context, which account for roughly three quarters of the total DNA methylation content in human and mouse cells. While the genomic distribution, inter-individual stability and functional role of CpG methylation are reasonably well understood, little is known about DNA methylation targeting CpA, CpC and CpT dinucleotides. Here we report a comprehensive analysis of non-CG methylation in 72 genome-scale DNA methylation maps across human pluripotent and differentiated cell types. We confirm non-CG methylation to be predominant in pluripotent cell types and observe an expected decrease upon differentiation and near complete absence in various differentiated cells. Our data highlight that non-CG methylation is highly variable and shows little conservation between different pluripotent cell lines. While we show a strong correlation of non-CG methylation and DNMT3 expression levels we find a statistical independence of non-CG methylation from pluripotency associated gene expression. Finally, non-CG methylation appears to be spatially correlated with CpG methylation. In summary these results contribute further to our understanding of DNA methylation in human cells and help clarify previous observations using a large representative sample set.
Project description:This SuperSeries is composed of the following subset Series: GSE30652: Recurrent Variations in DNA Methylation in Human Pluripotent Stem Cells and their Differentiated Derivatives [Illumina HT12v3 Gene Expression] GSE30653: Recurrent Variations in DNA Methylation in Human Pluripotent Stem Cells and their Differentiated Derivatives [Illumina Infinium 27K DNA Methylation] GSE31848: Recurrent Variations in DNA Methylation in Human Pluripotent Stem Cells and their Differentiated Derivatives [Illumina Infinium 450K DNA Methylation] Refer to individual Series
Project description:DNA methylation is an epigenetic modification that specifies the basic state of pluripotent stem cells and regulates the developmental transition from stem cells to various cell types. In flowering plants, the shoot apical meristem (SAM) contains a pluripotent stem cell population which generates the aerial part of plants including the germ cells. Under appropriate conditions, the SAM undergoes a developmental transition from a leaf-forming vegetative SAM to an inflorescence- and flower-forming reproductive SAM. While SAM characteristics are largely altered in this transition, the complete picture of DNA methylation remains elusive. Here, by analyzing whole-genome DNA methylation of isolated rice SAMs in the vegetative and reproductive stages, we found that methylation at CHH sites is kept high, particularly at transposable elements (TEs), in the vegetative SAM relative to the differentiated leaf, and increases in the reproductive SAM via the RNA-dependent DNA methylation pathway. We also found that half of the TEs that were highly methylated in gametes had already undergone CHH hypermethylation in the SAM. Our results indicate that changes in DNA methylation begin in the SAM long before germ cell differentiation to protect the genome from harmful TEs.