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

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 journal › Review article › peer-review

2 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 language	English (US)
Pages (from-to)	2624-2640
Number of pages	17
Journal	Molecular Cell
Volume	83
Issue number	15
DOIs	https://doi.org/10.1016/j.molcel.2023.06.018
State	Published - Aug 3 2023

All Science Journal Classification (ASJC) codes

Molecular Biology
Cell Biology

Keywords

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

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10.1016/j.molcel.2023.06.018

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Dekker, J., Alber, F., Aufmkolk, S., Beliveau, B. J., Bruneau, B. G., Belmont, A. S., Bintu, L., Boettiger, A., Calandrelli, R., Disteche, C. M., Gilbert, D. M., Gregor, T., Hansen, A. S., Huang, B., Huangfu, D., Kalhor, R., Leslie, C. S., Li, W., Li, Y., ... Zhong, S. (2023). Spatial and temporal organization of the genome: Current state and future aims of the 4D nucleome project. Molecular Cell, 83(15), 2624-2640. https://doi.org/10.1016/j.molcel.2023.06.018

@article{c94f22fd15c143a39af3eb54d095c3d0,

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

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",

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

note = "Funding Information: 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. Funding Information: 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). Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",

year = "2023",

month = aug,

day = "3",

doi = "10.1016/j.molcel.2023.06.018",

language = "English (US)",

volume = "83",

pages = "2624--2640",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "15",

}

Dekker, J, Alber, F, Aufmkolk, S, Beliveau, BJ, Bruneau, BG, Belmont, AS, Bintu, L, Boettiger, A, Calandrelli, R, Disteche, CM, Gilbert, DM, Gregor, T, Hansen, AS, Huang, B, Huangfu, D, Kalhor, R, Leslie, CS, Li, W, Li, Y, Ma, J, Noble, WS, Park, PJ, Phillips-Cremins, JE, Pollard, KS, Rafelski, SM, Ren, B, Ruan, Y, Shav-Tal, Y, Shen, Y, Shendure, J, Shu, X, Strambio-De-Castillia, C, Vertii, A, Zhang, H & Zhong, S 2023, 'Spatial and temporal organization of the genome: Current state and future aims of the 4D nucleome project', Molecular Cell, vol. 83, no. 15, pp. 2624-2640. https://doi.org/10.1016/j.molcel.2023.06.018

TY - JOUR

T1 - Spatial and temporal organization of the genome

T2 - Current state and future aims of the 4D nucleome project

AU - Dekker, Job

AU - Alber, Frank

AU - Aufmkolk, Sarah

AU - Beliveau, Brian J.

AU - Bruneau, Benoit G.

AU - Belmont, Andrew S.

AU - Bintu, Lacramioara

AU - Boettiger, Alistair

AU - Calandrelli, Riccardo

AU - Disteche, Christine M.

AU - Gilbert, David M.

AU - Gregor, Thomas

AU - Hansen, Anders S.

AU - Huang, Bo

AU - Huangfu, Danwei

AU - Kalhor, Reza

AU - Leslie, Christina S.

AU - Li, Wenbo

AU - Li, Yun

AU - Ma, Jian

AU - Noble, William S.

AU - Park, Peter J.

AU - Phillips-Cremins, Jennifer E.

AU - Pollard, Katherine S.

AU - Rafelski, Susanne M.

AU - Ren, Bing

AU - Ruan, Yijun

AU - Shav-Tal, Yaron

AU - Shen, Yin

AU - Shendure, Jay

AU - Shu, Xiaokun

AU - Strambio-De-Castillia, Caterina

AU - Vertii, Anastassiia

AU - Zhang, Huaiying

AU - Zhong, Sheng

N1 - Funding Information: 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. Funding Information: 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). Publisher Copyright: © 2023 Elsevier Inc.

PY - 2023/8/3

Y1 - 2023/8/3

N2 - 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.

AB - 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.

KW - 4D nucleome

KW - cell cycle

KW - chromosome folding

KW - development

KW - disease model

KW - genomics technologies

KW - imaging technologies

KW - modeling

KW - nuclear organization

UR - http://www.scopus.com/inward/record.url?scp=85166624218&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85166624218&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2023.06.018

DO - 10.1016/j.molcel.2023.06.018

M3 - Review article

C2 - 37419111

AN - SCOPUS:85166624218

SN - 1097-2765

VL - 83

SP - 2624

EP - 2640

JO - Molecular Cell

JF - Molecular Cell

IS - 15

ER -

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

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