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基因组的时空组织:4D 核组学项目的现状和未来目标。

Spatial and temporal organization of the genome: Current state and future aims of the 4D nucleome project.

机构信息

University of Massachusetts Chan Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.

University of California, Los Angeles, Los Angeles, CA, USA.

出版信息

Mol Cell. 2023 Aug 3;83(15):2624-2640. doi: 10.1016/j.molcel.2023.06.018. Epub 2023 Jul 6.

Abstract

The four-dimensional nucleome (4DN) consortium studies the architecture of the genome and the nucleus in space and time. We summarize progress by the consortium and highlight the development of technologies for (1) mapping genome folding and identifying roles of nuclear components and bodies, proteins, and RNA, (2) characterizing nuclear organization with time or single-cell resolution, and (3) imaging of nuclear organization. With these tools, the consortium has provided over 2,000 public datasets. Integrative computational models based on these data are starting to reveal connections between genome structure and function. We then present a forward-looking perspective and outline current aims to (1) delineate dynamics of nuclear architecture at different timescales, from minutes to weeks as cells differentiate, in populations and in single cells, (2) characterize cis-determinants and trans-modulators of genome organization, (3) test functional consequences of changes in cis- and trans-regulators, and (4) develop predictive models of genome structure and function.

摘要

四维度组蛋白(4DN)联盟研究基因组和细胞核在空间和时间上的结构。我们总结了联盟的进展,并强调了以下技术的发展:(1)绘制基因组折叠图谱并确定核成分和体、蛋白质和 RNA 的作用,(2)以时间或单细胞分辨率描述核组织,(3)核组织的成像。有了这些工具,联盟提供了 2000 多个公共数据集。基于这些数据的综合计算模型开始揭示基因组结构和功能之间的联系。然后,我们提出了前瞻性的观点,并概述了当前的目标,(1)描绘从几分钟到几周的不同时间尺度上细胞核结构的动力学,包括细胞分化时的群体和单细胞,(2)描述基因组组织的顺式决定因素和反式调节剂,(3)测试顺式和反式调节剂变化的功能后果,(4)开发基因组结构和功能的预测模型。

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