A DNA methylation atlas of normal human cell types
2023/01/04 by Netanel Loyfer, Judith Magenheim, Ayelet Peretz +50 · 647 citations
Biochemistry, Genetics and Molecular Biology · #Biology #Cancer-related gene regulation #Chromatin #Computational biology #CpG site #DNA #DNA methylation #Differentially methylated regions #Enhancer #Epigenetics #Epigenetics and DNA Methylation #Epigenetics of physical exercise #Epigenomics #Gene #Gene expression #Genetics #Methylation #RNA modifications and cancer #Regulation of gene expression
paper · pdf · doi:10.1038/s41586-022-05580-6
published in Nature 613(7943), 355-364 (Nature Portfolio)
openalex publication_date 2023/01/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06
Abstract
Abstract DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes 1 . 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 2–5 . 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. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. 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. 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.
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