The genome requires tight regulation in space and time to maintain viable cell functions. Advances in our understanding of the 3D genome show a complex hierarchical network of structures, involving compartments, membraneless bodies, topologically associating domains, lamina associated domains, protein- or RNA-mediated loops, enhancer-promoter contacts, and accessible chromatin regions, with chromatin state regulation through epigenetic and transcriptional mechanisms. Further technology developments are poised to increase genomic resolution, dissect single-cell behaviors, including in vivo dynamics of genome folding, and provide mechanistic perspectives that identify further 3D genome players by integrating multiomics information. We highlight recent key developments in 4D nucleome methodologies and give a perspective on their future directions.

中文翻译：

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4D 核组研究中不断发展的方法和概念。

基因组需要在空间和时间上进行严格调控以维持可行的细胞功能。我们对 3D 基因组理解的进展显示出复杂的分层结构网络，包括区室、无膜体、拓扑关联域、层相关域、蛋白质或 RNA 介导的环、增强子-启动子接触以及可及的染色质区域，以及染色质通过表观遗传和转录机制进行状态调节。进一步的技术发展有望提高基因组分辨率，剖析单细胞行为，包括基因组折叠的体内动力学，并提供通过整合多组学信息来识别更多 3D 基因组参与者的机制视角。我们重点介绍 4D 核组方法学的最新关键进展，并对其未来方向进行展望。