Beliveau Brian J, Akilesh Shreeram
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Nat Rev Nephrol. 2025 Feb;21(2):97-114. doi: 10.1038/s41581-024-00894-2. Epub 2024 Oct 15.
The human genome is tightly packed into the 3D environment of the cell nucleus. Rapidly evolving and sophisticated methods of mapping 3D genome architecture have shed light on fundamental principles of genome organization and gene regulation. The genome is physically organized on different scales, from individual genes to entire chromosomes. Nuclear landmarks such as the nuclear envelope and nucleoli have important roles in compartmentalizing the genome within the nucleus. Genome activity (for example, gene transcription) is also functionally partitioned within this 3D organization. Rather than being static, the 3D organization of the genome is tightly regulated over various time scales. These dynamic changes in genome structure over time represent the fourth dimension of the genome. Innovative methods have been used to map the dynamic regulation of genome structure during important cellular processes including organism development, responses to stimuli, cell division and senescence. Furthermore, disruptions to the 4D genome have been linked to various diseases, including of the kidney. As tools and approaches to studying the 4D genome become more readily available, future studies that apply these methods to study kidney biology will provide insights into kidney function in health and disease.
人类基因组被紧密包装在细胞核的三维环境中。快速发展且复杂的三维基因组结构测绘方法,已揭示了基因组组织和基因调控的基本原理。基因组在从单个基因到整条染色体的不同尺度上进行物理组织。诸如核膜和核仁等核地标在细胞核内对基因组进行分区方面发挥着重要作用。基因组活性(例如基因转录)在这种三维组织中也进行功能分区。基因组的三维组织并非静态,而是在各种时间尺度上受到严格调控。随着时间推移,基因组结构的这些动态变化代表了基因组的第四维。创新方法已被用于测绘重要细胞过程(包括生物体发育、对刺激的反应、细胞分裂和衰老)中基因组结构的动态调控。此外,四维基因组的破坏与包括肾脏疾病在内的各种疾病有关。随着研究四维基因组的工具和方法变得更容易获得,未来将这些方法应用于肾脏生物学研究的研究,将为健康和疾病状态下的肾脏功能提供见解。