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

Job Dekker; Frank Alber; Sarah Aufmkolk; Brian J Beliveau; Benoit G Bruneau; Andrew S Belmont; Lacramioara Bintu; Alistair Boettiger; Riccardo Calandrelli; Christine M Disteche; David M Gilbert; Thomas Gregor; Anders S Hansen; Bo Huang; Danwei Huangfu; Reza Kalhor; Christina S Leslie; Wenbo Li; Yun Li; Jian Ma; William S Noble; Peter J Park; Jennifer E Phillips-Cremins; Katherine S Pollard; Susanne M Rafelski; Bing Ren; Yijun Ruan; Yaron Shav-Tal; Yin Shen; Jay Shendure; Xiaokun Shu; Caterina Strambio-De-Castillia; Anastassiia Vertii; Huaiying Zhang; Sheng Zhong

doi:10.1016/j.molcel.2023.06.018

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

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

Authors

Job Dekker¹, Frank Alber², Sarah Aufmkolk³, Brian J Beliveau⁴, Benoit G Bruneau⁵, Andrew S Belmont⁶, Lacramioara Bintu⁷, Alistair Boettiger⁷, Riccardo Calandrelli⁸, Christine M Disteche⁴, David M Gilbert⁹, Thomas Gregor¹⁰, Anders S Hansen¹¹, Bo Huang¹², Danwei Huangfu¹³, Reza Kalhor¹⁴, Christina S Leslie¹³, Wenbo Li¹⁵, Yun Li¹⁶, Jian Ma¹⁷, William S Noble⁴, Peter J Park³, Jennifer E Phillips-Cremins¹⁸, Katherine S Pollard¹⁹, Susanne M Rafelski²⁰, Bing Ren⁸, Yijun Ruan²¹, Yaron Shav-Tal²², Yin Shen¹², Jay Shendure⁴, Xiaokun Shu¹², Caterina Strambio-De-Castillia²³, Anastassiia Vertii²³, Huaiying Zhang¹⁷, Sheng Zhong²⁴

Affiliations

¹ University of Massachusetts Chan Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: [email protected].
² University of California, Los Angeles, Los Angeles, CA, USA.
³ Harvard Medical School, Boston, MA, USA.
⁴ University of Washington, Seattle, WA, USA.
⁵ Gladstone Institutes, San Francisco, CA, USA; University of California, San Francisco, San Francisco, CA, USA.
⁶ University of Illinois Urbana-Champaign, Urbana, IL, USA.
⁷ Stanford University, Stanford, CA, USA.
⁸ University of California, San Diego, La Jolla, CA, USA.
⁹ San Diego Biomedical Research Institute, San Diego, CA, USA.
¹⁰ Princeton University, Princeton, NJ, USA.
¹¹ Massachusetts Institute of Technology, Cambridge, MA, USA.
¹² University of California, San Francisco, San Francisco, CA, USA.
¹³ Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁴ Johns Hopkins University, Baltimore, MD, USA.
¹⁵ University of Texas Health Science Center at Houston, Houston, TX, USA.
¹⁶ University of North Carolina, Gillings School of Global Public Health, Chapel Hill, NC, USA.
¹⁷ Carnegie Mellon University, Pittsburgh, PA, USA.
¹⁸ University of Pennsylvania, Philadelphia, PA, USA.
¹⁹ Gladstone Institutes, San Francisco, CA, USA; University of California, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, San Francisco, CA, USA.
²⁰ Allen Institute, Seattle, WA, USA.
²¹ Zhejiang University, Hangzhou, Zhejiang, China.
²² Bar-Ilan University, Ramat Gan, Israel.
²³ University of Massachusetts Chan Medical School, Boston, MA, USA.
²⁴ University of California, San Diego, La Jolla, CA, USA. Electronic address: [email protected].

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.

Keywords: 4D nucleome; cell cycle; chromosome folding; development; disease model; genomics technologies; imaging technologies; modeling; nuclear organization.

Publication types

Review
Research Support, N.I.H., Extramural

MeSH terms

Cell Nucleus* / genetics
Cell Nucleus* / metabolism
Chromatin / metabolism
Genome* / genetics

Substances

Chromatin

Abstract

Publication types

MeSH terms

Substances

Grants and funding