Benjamin Glaser - A DNA methylation atlas of normal human cell types
A DNA methylation atlas of normal human cell types
https://pubmed.ncbi.nlm.nih.gov/36599988/
Netanel Loyfer # 1, Judith Magenheim # 2, Ayelet Peretz # 2, Gordon Cann 3, Joerg Bredno 3, Agnes Klochendler 2, Ilana Fox-Fisher 2, Sapir Shabi-Porat 1, Merav Hecht 2, Tsuria Pelet 2, Joshua Moss 2 4, Zeina Drawshy 2, Hamed Amini 3, Patriss Moradi 3, Sudharani Nagaraju 3, Dvora Bauman 5, David Shveiky 5, Shay Porat 5, Uri Dior 5, Gurion Rivkin 6, Omer Or 6, Nir Hirshoren 7, Einat Carmon 8 9, Alon Pikarsky 10, Abed Khalaileh 8, Gideon Zamir 8, Ronit Grinbaum 8, Machmud Abu Gazala 8, Ido Mizrahi 8, Noam Shussman 8, Amit Korach 11, Ori Wald 11, Uzi Izhar 11, Eldad Erez 11, Vladimir Yutkin 12, Yaacov Samet 13, Devorah Rotnemer Golinkin 14, Kirsty L Spalding 15, Henrik Druid 16 17, Peter Arner 18, A M James Shapiro 19, Markus Grompe 20, Alex Aravanis 3 21, Oliver Venn 3, Arash Jamshidi 3, Ruth Shemer 2, Yuval Dor 22, Benjamin Glaser 23, Tommy Kaplan 24 25
Affiliations Expand
- PMID: 36599988
- PMCID: PMC9811898
Abstract
DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes1. 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 cells2-5. 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.