Department of Genetics, Stanford University School of Medicine, Palo Alto, CA, USA.
Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA.
Nature. 2020 Jul;583(7818):737-743. doi: 10.1038/s41586-020-2151-x. Epub 2020 Jul 29.
Physical interactions between distal regulatory elements have a key role in regulating gene expression, but the extent to which these interactions vary between cell types and contribute to cell-type-specific gene expression remains unclear. Here, to address these questions as part of phase III of the Encyclopedia of DNA Elements (ENCODE), we mapped cohesin-mediated chromatin loops, using chromatin interaction analysis by paired-end tag sequencing (ChIA-PET), and analysed gene expression in 24 diverse human cell types, including core ENCODE cell lines. Twenty-eight per cent of all chromatin loops vary across cell types; these variations modestly correlate with changes in gene expression and are effective at grouping cell types according to their tissue of origin. The connectivity of genes corresponds to different functional classes, with housekeeping genes having few contacts, and dosage-sensitive genes being more connected to enhancer elements. This atlas of chromatin loops complements the diverse maps of regulatory architecture that comprise the ENCODE Encyclopedia, and will help to support emerging analyses of genome structure and function.
远端调控元件之间的物理相互作用在调节基因表达中起着关键作用，但这些相互作用在细胞类型之间的变化程度以及它们对细胞类型特异性基因表达的贡献仍不清楚。在这里，作为 DNA 元件百科全书 (ENCODE) 第三阶段的一部分，我们使用通过末端配对标签测序的染色质相互作用分析 (ChIA-PET) 绘制了黏着蛋白介导的染色质环，并在 24 种不同的人类细胞类型（包括核心 ENCODE 细胞系）中分析了基因表达。所有染色质环中有 28%在细胞类型之间存在差异；这些差异与基因表达的变化适度相关，并能有效地根据其组织来源对细胞类型进行分组。基因的连接性与不同的功能类别相对应，管家基因的接触较少，而剂量敏感基因与增强子元件的连接更多。这个染色质环图谱补充了构成 ENCODE 百科全书的多样化调控结构图谱，并将有助于支持对基因组结构和功能的新兴分析。
