Simultaneous profiling of 3D genome structure and DNA methylation in single human cells
Simultaneous profiling of 3D genome structure and DNA methylation in single human cells
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DOI：
10.1038/s41592-019-0547-z
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发表时间：
2019-10-01
期刊：
影响因子：
48
通讯作者：
Ecker, Joseph R.
中科院分区：
文献类型：
--
作者：
Lee, Dong-Sung;Luo, Chongyuan;Ecker, Joseph R.
动态三维染色质构象是发育和疾病过程中基因调控的关键机制。尽管如此，从具有细胞类型特异性分辨率的复杂组织中分析三维基因组结构仍然具有挑战性。最近的研究表明，细胞类型特异性的表观基因组特征可以在复杂组织中使用单细胞测定来解决。然而，目前尚不清楚单细胞染色质构象捕获（3C）或Hi-C谱是否可以有效地识别细胞类型并重建细胞类型特异性染色质构象图。为了应对这些挑战，我们开发了单核甲基- 3c测序，以捕获染色质组织和DNA甲基化信息，并强有力地分离异质细胞类型。应用该方法，我们重建了14种皮层细胞类型的细胞类型特异性染色质构象图。这些数据集揭示了细胞类型特异性染色质构象和差异DNA甲基化之间的全基因组关联，表明调控基因表达的表观遗传过程之间普遍存在相互作用。
Dynamic three-dimensional chromatin conformation is a critical mechanism for gene regulation during development and disease. Despite this, profiling of three-dimensional genome structure from complex tissues with cell-type specific resolution remains challenging. Recent efforts have demonstrated that cell-type specific epigenomic features can be resolved in complex tissues using single-cell assays. However, it remains unclear whether single-cell chromatin conformation capture (3C) or Hi-C profiles can effectively identify cell types and reconstruct cell-type specific chromatin conformation maps. To address these challenges, we have developed single-nucleus methyl-3C sequencing to capture chromatin organization and DNA methylation information and robustly separate heterogeneous cell types. Applying this method to >4,200 single human brain prefrontal cortex cells, we reconstruct cell-type specific chromatin conformation maps from 14 cortical cell types. These datasets reveal the genome-wide association between cell-type specific chromatin conformation and differential DNA methylation, suggesting pervasive interactions between epigenetic processes regulating gene expression.