以色列耶路撒冷希伯来大学Tommy Kaplan、Benjamin Glaser和Yuval Dor共同合作，近期取得重要工作进展。他们研究绘制了正常人类细胞类型的DNA甲基化图谱。相关论文2023年1月4日在线发表于《自然》杂志上。
据介绍，DNA甲基化是控制基因表达和染色质组装的一个基本表观遗传标记，从而为细胞特性和发育过程提供了一个窗口。目前的数据集通常只包括一部分甲基化位点，而且往往是基于在培养过程中发生了巨大变化的细胞系，或基于含有不确定细胞混合物的组织。
研究人员描述了一个基于亚硫酸氢盐全基因组深度测序的人类甲基组图谱，该图谱允许对从205个健康组织样本中分拣出来的39种细胞类型的数千个独特标记物进行片段级分析。相同细胞类型的复制体有99.5%以上是相同的，表明细胞身份程序对环境扰动的稳健性。图谱的无监督聚类概括了组织个体发育的关键要素，并确定了自胚胎发育以来保留的甲基化模式。单个细胞类型中独特的非甲基化位点通常存在于转录增强子中，并含有组织特异性转录调节因子的DNA结合位点。独特的超甲基化位点是罕见的，并且富含CpG岛、多梳靶标和CTCF结合位点，这表明在形成细胞类型特异性染色质环中发挥了新的作用。
总之，该图谱为研究基因调控和疾病相关基因变异提供了重要资源，并为液体活检提供了大量潜在的组织特异性生物标志物。
附：英文原文
Title: A DNA methylation atlas of normal human cell types
Author: Loyfer, Netanel, Magenheim, Judith, Peretz, Ayelet, Cann, Gordon, Bredno, Joerg, Klochendler, Agnes, Fox-Fisher, Ilana, Shabi-Porat, Sapir, Hecht, Merav, Pelet, Tsuria, Moss, Joshua, Drawshy, Zeina, Amini, Hamed, Moradi, Patriss, Nagaraju, Sudharani, Bauman, Dvora, Shveiky, David, Porat, Shay, Dior, Uri, Rivkin, Gurion, Or, Omer, Hirshoren, Nir, Carmon, Einat, Pikarsky, Alon, Khalaileh, Abed, Zamir, Gideon, Grinbaum, Ronit, Abu Gazala, Machmud, Mizrahi, Ido, Shussman, Noam, Korach, Amit, Wald, Ori, Izhar, Uzi, Erez, Eldad, Yutkin, Vladimir, Samet, Yaacov, Rotnemer Golinkin, Devorah, Spalding, Kirsty L., Druid, Henrik, Arner, Peter, Shapiro, A. M. James, Grompe, Markus, Aravanis, Alex, Venn, Oliver, Jamshidi, Arash, Shemer, Ruth, Dor, Yuval, Glaser, Benjamin, Kaplan, Tommy
Issue&Volume: 2023-01-04
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 cells2,3,4,5. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39cell types sorted from 205healthy 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.
DOI: 10.1038/s41586-022-05580-6
Source: https://www.nature.com/articles/s41586-022-05580-6
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
