4.8 Article

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

Journal

MOLECULAR CELL
Volume 83, Issue 15, Pages 2624-2640

Publisher

CELL PRESS
DOI: 10.1016/j.molcel.2023.06.018

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The four-dimensional nucleome (4DN) consortium investigates the structure and temporal-spatial characteristics of the genome and nucleus. The consortium has made significant progress in mapping genome folding, identifying nuclear components and bodies, and imaging nuclear organization. The generated datasets have been used to develop computational models that reveal connections between genome structure and function. Future aims include studying dynamics of nuclear architecture, understanding cis-determinants and trans-modulators of genome organization, exploring functional consequences of changes in regulators, and developing predictive models
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) char-acterize 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.

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