美国西北大学岳峰小组近日取得一项新成果。经过不懈努力，他们的最新研究提出了人类4D核组的结构和功能的综合视图。相关论文发表在2025年12月17日出版的《自然》杂志上。

在这里，课题组描述了4D核体项目（4D Nucleome project）在广泛主题的H1人胚胎干细胞和永活成纤维细胞（HFFc6）中绘制和分析4D核体的努力。该课题组制作并整合了4D核组的各种基因组数据集，每个数据集都提供了独特的观察结果，这使他们能够组装每种细胞类型超过14万个环相互作用的广泛目录，以生成染色体结构域类型及其亚核位置的详细分类和注释，并获得所有基因的核环境的单细胞3D模型，包括它们与远端元件的远程相互作用。

通过广泛的基准测试，研究小组描述了研究4D核组的不同基因组分析的独特优势，为未来的研究提供指导。基于群体和个体细胞间基因组结构变化的三维模型显示了染色体折叠、核组织、染色质环、基因转录和DNA复制之间的联系。最后，课题组研究人员展示了从DNA序列预测基因组折叠的计算方法的主题，这将有助于发现遗传变异（包括与疾病相关的变异）对基因组结构和功能的潜在影响。

据悉，人类基因组（4D核组）的动态三维（3D）组织与基因组功能有关。

附：英文原文

Title: An integrated view of the structure and function of the human 4D nucleome

Author: Dekker, Job, Oksuz, Betul Akgol, Zhang, Yang, Wang, Ye, Minsk, Miriam K., Kuang, Shuzhen, Yang, Liyan, Gibcus, Johan H., Krietenstein, Nils, Rando, Oliver J., Xu, Jie, Janssens, Derek H., Henikoff, Steven, Kukalev, Alexander, Andra, Willemin, Winick-Ng, Warren, Kempfer, Rieke, Pombo, Ana, Yu, Miao, Kumar, Pradeep, Zhang, Liguo, Belmont, Andrew S., Sasaki, Takayo, van Schaik, Tom, Brueckner, Laura, Peric-Hupkes, Daan, van Steensel, Bas, Wang, Ping, Chai, Haoxi, Kim, Minji, Ruan, Yijun, Zhang, Ran, Quinodoz, Sofia A., Bhat, Prashant, Guttman, Mitchell, Zhao, Wenxin, Chien, Shu, Liu, Yuan, Venev, Sergey V., Plewczynski, Dariusz, Azcarate, Ibai Irastorza, Szab, Dominik, Thieme, Christoph J., Szczepiska, Teresa, Chiliski, Mateusz, Sengupta, Kaustav, Conte, Mattia, Esposito, Andrea, Abraham, Alex, Zhang, Ruochi, Wang, Yuchuan, Wen, Xingzhao, Wu, Qiuyang, Yang, Yang, Liu, Jie, Boninsegna, Lorenzo, Yildirim, Asli, Zhan, Yuxiang, Chiariello, Andrea Maria, Bianco, Simona, Lee, Lindsay, Hu, Ming, Li, Yun, Barnett, R. Jordan, Cook, Ashley L., Emerson, Daniel J., Marchal, Claire, Zhao, Peiyao, Park, Peter J.

Issue&Volume: 2025-12-17

Abstract: The dynamic three-dimensional (3D) organization of the human genome (the 4D nucleome) is linked to genome function. Here we describe efforts by the 4D Nucleome Project1 to map and analyse the 4D nucleome in widely used H1 human embryonic stem cells and immortalized fibroblasts (HFFc6). We produced and integrated diverse genomic datasets of the 4D nucleome, each contributing unique observations, which enabled us to assemble extensive catalogues of more than 140,000 looping interactions per cell type, to generate detailed classifications and annotations of chromosomal domain types and their subnuclear positions, and to obtain single-cell 3D models of the nuclear environment of all genes including their long-range interactions with distal elements. Through extensive benchmarking, we describe the unique strengths of different genomic assays for studying the 4D nucleome, providing guidelines for future studies. Three-dimensional models of population-based and individual cell-to-cell variation in genome structure showed connections between chromosome folding, nuclear organization, chromatin looping, gene transcription and DNA replication. Finally, we demonstrate the use of computational methods to predict genome folding from DNA sequence, which will facilitate the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

DOI: 10.1038/s41586-025-09890-3

Source: https://www.nature.com/articles/s41586-025-09890-3