Exploring chromosomal structural heterogeneity across multiple cell lines

Abstract
Data availability
Article and author information
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Abstract

Using computer simulations, we generate cell-specific 3D chromosomal structures and compare them to recently published chromatin structures obtained through microscopy. We demonstrate using machine learning and polymer physics simulations that epigenetic information can be used to predict the structural ensembles of multiple human cell lines. Theory predicts that chromosome structures are fluid and can only be described by an ensemble, which is consistent with the observation that chromosomes exhibit no unique fold. Nevertheless, our analysis of both structures from simulation and microscopy reveals that short segments of chromatin make two-state transitions between closed conformations and open dumbbell conformations. Finally, we study the conformational changes associated with the switching of genomic compartments observed in human cell lines. The formation of genomic compartments resembles hydrophobic collapse in protein folding, with the aggregation of denser and predominantly inactive chromatin driving the positioning of active chromatin toward the surface of individual chromosomal territories.

Data availability

All of the simulated chromosome structures have been deposited in the Nucleome Data Bank (https://ndb.rice.edu/Data).

The following data sets were generated

(2020) Cheng_etal_H1-hESC_2020
Nucleome Data Bank, Cheng_etal_H1-hESC_2020.

https://ndb.rice.edu/static/structures/download/Cheng_etal_H1-hESC_2020/
(2020) Cheng_etal_HUVEC_2020
Nucleome Data Bank, Cheng_etal_HUVEC_2020.

https://ndb.rice.edu/static/structures/download/Cheng_etal_HUVEC_2020/
(2020) Cheng_etal_HMEC_2020
Nucleome Data Bank, Cheng_etal_HMEC_2020.

https://ndb.rice.edu/static/structures/download/Cheng_etal_HMEC_2020/
(2020) Cheng_etal_Hela-S3_2020
Nucleome Data Bank, Cheng_etal_Hela-S3_2020.

https://ndb.rice.edu/static/structures/download/Cheng_etal_Hela-S3_2020/
(2020) Cheng_etal_IMR90_2020
Nucleome Data Bank, Cheng_etal_IMR90_2020.

https://ndb.rice.edu/static/structures/download/Cheng_etal_IMR90_2020/
(2020) Cheng_etal_K562_2020
Nucleome Data Bank, Cheng_etal_K562_2020.

https://ndb.rice.edu/static/structures/download/Cheng_etal_K562_2020/

The following previously published data sets were used

1. Bintu B
2. Mateo LJ
3. Su J
4. Sinnott-Armstrong NA
5. Parker M
6. Kinrot S
7. Yamaya K
8. Boettiger AN
9. Zhuang X
(2018) IMR90_chr21-18-20Mb.csv
IMR90_chr21-18-20Mb.csv.

https://github.com/BogdanBintu/ChromatinImaging/tree/master/Data
1. Bintu B
2. Mateo LJ
3. Su J
4. Sinnott-Armstrong NA
5. Parker M
6. Kinrot S
7. Yamaya K
8. Boettiger AN
9. Zhuang X
(2018) IMR90_chr21-28-30Mb.csv
IMR90_chr21-28-30Mb.csv.

https://github.com/BogdanBintu/ChromatinImaging/tree/master/Data
1. Bintu B
2. Mateo LJ
3. Su J
4. Sinnott-Armstrong NA
5. Parker M
6. Kinrot S
7. Yamaya K
8. Boettiger AN
9. Zhuang X
(2018) K562_chr21-28-30Mb.csv
K562_chr21-28-30Mb.csv.

https://github.com/BogdanBintu/ChromatinImaging/tree/master/Data

Article and author information

Author details

Ryan R Cheng

Center for Theoretical Biological Physics, Rice University, Houston, United States

For correspondence
ryan.r.cheng@gmail.com

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6378-295X
Vinicius Contessoto

Brazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, Brazil

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1891-9563
Erez Lieberman-Aiden

Baylor College of Medicine, Houston, United States

Competing interests
The authors declare that no competing interests exist.
Peter G Wolynes

Center for Theoretical Biological Physics, Rice University, Houston, United States

Competing interests
The authors declare that no competing interests exist.
Michele Di Pierro

Department of Physics, Northeastern University, Boston, United States

For correspondence
m.dipierro@northeastern.edu

Competing interests
The authors declare that no competing interests exist.
Jose N Onuchic

Center for Theoretical Biological Physics and Department of Physics, Rice University, Houston, United States

For correspondence
jonuchic@rice.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9448-0388

Funding

National Science Foundation (PHY-1427654)

Ryan R Cheng
Vinicius Contessoto
Erez Lieberman-Aiden
Peter G Wolynes
Michele Di Pierro
Jose N Onuchic

NHGRI Center for Excellence for Genomic Sciences (HG006193)

Erez Lieberman-Aiden

Welch Foundation (Q-1866)

Erez Lieberman-Aiden

Cancer Prevention and Research Institute of Texas (R1304)

Erez Lieberman-Aiden

NIH Office of the Director (U01HL130010)

Erez Lieberman-Aiden

NIH Office of the Director (UM1HG009375)

Erez Lieberman-Aiden

NVIDIA Research Center Award

Erez Lieberman-Aiden

IBM University Challenge Award

Erez Lieberman-Aiden

Google Research Award

Erez Lieberman-Aiden

McNair Medical Institute Scholar

Erez Lieberman-Aiden

President's Early Career in Science and Engineering

Erez Lieberman-Aiden

National Science Foundation (CHE-1614101)

Jose N Onuchic

Welch Foundation (C-1792)

Jose N Onuchic

Cancer Prevention and Research Institute of Texas

Jose N Onuchic

Welch Foundation

Vinicius Contessoto

Sao Paulo Research Foundation and Higher Education Personnel (2016/13998-8)

Vinicius Contessoto

Higher Education Personnel Improvement Coordination (2017/09662-7)

Vinicius Contessoto

D. R. Bullard-Welch Chair at Rice University (Grant C-0016)

Peter G Wolynes

NIH Office of the Director (1DP2OD008540-01)

Erez Lieberman-Aiden

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.