Exploring chromosomal structural heterogeneity across multiple cell lines
- Rice University, United States
- Brazilian Center for Research in Energy and Materials, Brazil
- Baylor College of Medicine, United States
- Northeastern University, United States
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).
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Cheng_etal_H1-hESC_2020Nucleome Data Bank, Cheng_etal_H1-hESC_2020.
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Cheng_etal_HUVEC_2020Nucleome Data Bank, Cheng_etal_HUVEC_2020.
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Cheng_etal_HMEC_2020Nucleome Data Bank, Cheng_etal_HMEC_2020.
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Cheng_etal_Hela-S3_2020Nucleome Data Bank, Cheng_etal_Hela-S3_2020.
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Cheng_etal_IMR90_2020Nucleome Data Bank, Cheng_etal_IMR90_2020.
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Cheng_etal_K562_2020Nucleome Data Bank, Cheng_etal_K562_2020.
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IMR90_chr21-18-20Mb.csvIMR90_chr21-18-20Mb.csv.
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IMR90_chr21-28-30Mb.csvIMR90_chr21-28-30Mb.csv.
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K562_chr21-28-30Mb.csvK562_chr21-28-30Mb.csv.
Article and author information
Author details
Vinicius Contessoto
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.
Reviewing Editor
- Yibing Shan, DE Shaw Research, United States
Version history
- Received: June 22, 2020
- Accepted: October 8, 2020
- Accepted Manuscript published: October 13, 2020 (version 1)
- Version of Record published: October 28, 2020 (version 2)
Copyright
© 2020, Cheng et al.
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.
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Exploring chromosomal structural heterogeneity across multiple cell lines
eLife 9:e60312.
https://doi.org/10.7554/eLife.60312
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