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 MaWilliam 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

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations

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.

Original languageEnglish
Pages (from-to)2624-2640
Number of pages17
JournalMolecular Cell
Volume83
Issue number15
DOIs
StatePublished - 3 Aug 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Inc.

Funding

This work is funded by the following NIH Common Fund 4D Nucleome grants : U54DK107980 and UM1HG011536 awarded to J.D., UM1HG011593 awarded to J.M. and F.A., U01HL157989 awarded to B.G.B. and K.S.P., U01DK127422 awarded to A.S.B., U01DK127419 awarded to L.B. and A.B., U01DK127429 awarded to T.G., U01DK127421 awarded to B.H. and X.S., U01DK128852 awarded to D.H. and C.S.L., U01HL156056 awarded to R.K., U01HL156059 awarded to W.L., UM1HG011586 awarded to W.S.N. and J.S., U01CA200059 awarded to P.J.P., U01DK127405 and U01DA052715 awarded to J.E.P-C., UM1HG011585 awarded to B.R., U01DA052713 awarded to Y.S., U01CA260851 awarded to H.Z., and U01CA200147 awarded to S.Z. J.D. is an investigator of the Howard Hughes Medical Institute. B.H. is a Chan Zuckerberg Biohub – San Francisco investigator. S.A. as a member of the Chao-Ting Wu laboratory is funded by R01HD091797 and 5RM1HG011016-02 awarded to Chao-Ting Wu. This work is funded by the following NIH Common Fund 4D Nucleome grants: U54DK107980 and UM1HG011536 awarded to J.D. UM1HG011593 awarded to J.M. and F.A. U01HL157989 awarded to B.G.B. and K.S.P. U01DK127422 awarded to A.S.B. U01DK127419 awarded to L.B. and A.B. U01DK127429 awarded to T.G. U01DK127421 awarded to B.H. and X.S. U01DK128852 awarded to D.H. and C.S.L. U01HL156056 awarded to R.K. U01HL156059 awarded to W.L. UM1HG011586 awarded to W.S.N. and J.S. U01CA200059 awarded to P.J.P. U01DK127405 and U01DA052715 awarded to J.E.P-C. UM1HG011585 awarded to B.R. U01DA052713 awarded to Y.S. U01CA260851 awarded to H.Z. and U01CA200147 awarded to S.Z. J.D. is an investigator of the Howard Hughes Medical Institute. B.H. is a Chan Zuckerberg Biohub – San Francisco investigator. S.A. as a member of the Chao-Ting Wu laboratory is funded by R01HD091797 and 5RM1HG011016-02 awarded to Chao-Ting Wu. J.D. is on the Scientific Advisory Board of Arima Genomics (San Diego, CA) and Omega Therapeutics (Cambridge, MA). F.A. is a shareholder of EarlyDiagnostics, Inc. S.A. is a member of the Chao-Ting Wu laboratory and holds or has patent filings pertaining to imaging and has held a sponsored research agreement with Bruker Inc. L.B. is a co-founder and scientific advisor of Stylus Medicine (Cambridge, MA). W.L. is a co-founder of Hub Biosciences. B.R. is a co-founder of and member of the Scientific Advisory Board of Arima Genomics (San Diego, CA) and a co-founder of Epigenome Technologies (San Diego, CA). J.S. is a Scientific Advisory Board member, consultant, and/or co-founder of Cajal Neuroscience, Guardant Health, Maze Therapeutics, Camp4 Therapeutics, Phase Genomics, Adaptive Biotechnologies, Scale Biosciences, Sixth Street Capital, Pacific Biosciences, and Prime Medicine. X.S. is a co-founder of Granule Therapeutics (San Francisco, CA). S.Z. is a founder and board member of Genemo, Inc (San Diego, CA).

FundersFunder number
Epigenome Technologies
Omega Therapeutics
National Institutes of HealthUM1HG011536, U01HL156059, U01DA052713, U01HL156056, U01CA200059, U01CA200147, U01DK127405, U01DK127429, U01DK127419, U01CA260851, U01DK127421, U01DK128852, U01DK127422, UM1HG011593, UM1HG011585, UM1HG011586, U01DA052715, U54DK107980, U01HL157989
Howard Hughes Medical InstituteR01HD091797, 5RM1HG011016-02
scientific advisor of Stylus Medicine

    Keywords

    • 4D nucleome
    • cell cycle
    • chromosome folding
    • development
    • disease model
    • genomics technologies
    • imaging technologies
    • modeling
    • nuclear organization

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