Systematic identification and annotation of human methylation marks based on bisulfite sequencing methylomes reveals distinct roles of cell type-specific hypomethylation in the regulation of cell identity genes.
Systematic identification and annotation of human methylation marks based on bisulfite sequencing methylomes reveals distinct roles of cell type-specific hypomethylation in the regulation of cell identity genes.
复制标题
基于亚硫酸氢盐测序甲基化组的人类甲基化标记的系统识别和注释揭示了细胞类型特异性低甲基化在细胞身份基因调节中的独特作用
DOI：
10.1093/nar/gkv1332
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发表时间：
2016-01-08
影响因子：
14.9
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Liu H;Liu X;Zhang S;Lv J;Li S;Shang S;Jia S;Wei Y;Wang F;Su J;Wu Q;Zhang Y
DNA甲基化是多细胞真核生物基因调控的关键表观遗传标记。虽然各种人类细胞类型可能具有相同的基因组，但这些细胞具有不同的甲基化组。跨细胞类型的甲基化标记的系统鉴定和表征对于理解细胞命运决定的复杂调控网络至关重要。在这项研究中，我们提出了一个基于熵的框架，称为SMART整合全基因组亚硫酸氢盐测序甲基化组在42个人类组织/细胞，并确定了757 887个基因组片段。近75%的片段在所有细胞类型中显示出均匀的甲基化。从剩下的25%的片段中，我们使用统计方法鉴定了在少数细胞类型中特异性低/高甲基化的细胞类型特异性低/高甲基化标记，并提供了人类甲基化标记的图谱。进一步分析表明，H3 K27 ac和转录因子结合位点以细胞类型特异的方式富集了细胞类型特异的低甲基化标记。特别地，我们观察到细胞类型特异性低甲基化标记与驱动细胞身份基因表达的细胞类型特异性超级增强子相关。该框架提供了人类基因组的互补功能注释，并有助于阐明细胞类型特异性低甲基化的关键特征和功能。
DNA methylation is a key epigenetic mark that is critical for gene regulation in multicellular eukaryotes. Although various human cell types may have the same genome, these cells have different methylomes. The systematic identification and characterization of methylation marks across cell types are crucial to understand the complex regulatory network for cell fate determination. In this study, we proposed an entropy-based framework termed SMART to integrate the whole genome bisulfite sequencing methylomes across 42 human tissues/cells and identified 757 887 genome segments. Nearly 75% of the segments showed uniform methylation across all cell types. From the remaining 25% of the segments, we identified cell type-specific hypo/hypermethylation marks that were specifically hypo/hypermethylated in a minority of cell types using a statistical approach and presented an atlas of the human methylation marks. Further analysis revealed that the cell type-specific hypomethylation marks were enriched through H3K27ac and transcription factor binding sites in cell type-specific manner. In particular, we observed that the cell type-specific hypomethylation marks are associated with the cell type-specific super-enhancers that drive the expression of cell identity genes. This framework provides a complementary, functional annotation of the human genome and helps to elucidate the critical features and functions of cell type-specific hypomethylation.