An Integrated View of the Structure and Function of the Human 4D Nucleome

4D Nucleome Consortium,Job Dekker， William S Noble,Feng Yue

bioRxiv the preprint server for biology（2024）

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Abstract

The dynamic three-dimensional (3D) organization of the human genome (the 4D Nucleome) is closely linked to genome function. Here, we integrate a wide variety of genomic data generated by the 4D Nucleome Project to provide a detailed view of human 3D genome organization in widely used embryonic stem cells (H1-hESCs) and immortalized fibroblasts (HFFc6). We provide extensive benchmarking of 3D genome mapping assays and integrate these diverse datasets to annotate spatial genomic features across scales. The data reveal a rich complexity of chromatin domains and their sub-nuclear positions, and over one hundred thousand structural loops and promoter-enhancer interactions. We developed 3D models of population-based and individual cell-to-cell variation in genome structure, establishing connections between chromosome folding, nuclear organization, chromatin looping, gene transcription, and DNA replication. We demonstrate the use of computational methods to predict genome folding from DNA sequence, uncovering potential effects of genetic variants on genome structure and function. Together, this comprehensive analysis contributes insights into human genome organization and enhances our understanding of connections between the regulation of genome function and 3D genome organization in general.

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【要点】：本文通过整合4D Nucleome项目产生的多种基因组数据，揭示了人类三维基因组组织结构的复杂性和与基因功能的联系，为理解基因组调控与三维结构的关系提供了新的视角。

【方法】：研究团队综合运用了多种三维基因组映射技术，并通过生物信息学方法对数据进行整合和注释，建立基于群体的以及单个细胞间基因组结构变异的三维模型。

【实验】：实验使用了H1-hESCs和HFFc6两种细胞系，通过广泛的基准测试来评估三维基因组映射技术的准确性，并发现了超过十万个结构环和启动子-增强子相互作用，实验数据集名称未在摘要中明确提及，但据论文标题推测应与4D Nucleome项目相关。研究还展示了计算方法预测基因组折叠的能力，以及基因变异对基因组结构与功能的潜在影响。