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Atlas hebrew font free download4/3/2024 ![]() As a partial solution, recent studies used single-cell RNA sequencing data from whole tissues to identify marker genes expressed in specific cell types, then identified specific CpGs whose methylation is anticorrelated with expression. Most DNA methylation analyses interrogated primarily bulk tissue, thus precluding the study of minority cell types such as tissue-resident immune cells, fibroblasts or endothelial cells, whereas others analysed cultured cells, which may contain nonphysiological methylation patterns introduced in vitro 13. In addition, by measuring each CpG site independently, such assays overlook coordinated patterns of DNA methylation occurring in blocks, the critical functional units of DNA methylation 11, 12. Multiple studies that have characterized methylomes of embryonic development, differentiation, cancer or other settings 6, 7, 8, 9 have relied on the Illumina BeadChip platforms, which are limited to a predefined subset of 450,000 or 860,000 CpG methylation sites, representing just 3% of around 30 million CpG sites in the human genome 10. Underneath these lies DNA methylation, a stable epigenetic mark that underpins the lifelong maintenance of cellular identity.Īvailable human DNA methylation datasets suffer from major limitations. Gene expression, DNA accessibility and chromatin packaging are well-established essential determinants of cellular phenotype. Understanding how the same DNA sequence is interpreted differently in different cell types is a fundamental challenge of biology. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. ![]() Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. ![]() ![]() ![]() Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells 2, 3, 4, 5. Nature volume 613, pages 355–364 ( 2023) Cite this articleĭNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes 1. A DNA methylation atlas of normal human cell types ![]()
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