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A human DNA methylation atlas reveals principles of cell type-specific methylation and identifies thousands of cell type-specific regulatory elements

ABSTRACT: DNA methylation is a fundamental epigenetic mark that governs chromatin organization, cell identity, and gene expression. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing of 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are >99.5% identical, demonstrating robustness of cell identity programs to genetic variation and environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny, and identifies methylation patterns retained since gastrulation. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely methylated loci are rare and are enriched for CpG islands, polycomb targets, and CTCF binding sites, suggesting a role in shaping cell type-specific chromatin looping. The atlas provides an essential resource for interpretation of disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE186458 | GEO | 2022/03/02

REPOSITORIES: GEO

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