1. Chromosomes and Gene Expression
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Exploring chromosomal structural heterogeneity across multiple cell lines

  1. Ryan R Cheng  Is a corresponding author
  2. Vinicius Contessoto
  3. Erez Lieberman-Aiden
  4. Peter G Wolynes
  5. Michele Di Pierro  Is a corresponding author
  6. Jose N Onuchic  Is a corresponding author
  1. Rice University, United States
  2. Brazilian Center for Research in Energy and Materials, Brazil
  3. Baylor College of Medicine, United States
  4. Northeastern University, United States
Research Article
  • Cited 9
  • Views 1,527
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Cite this article as: eLife 2020;9:e60312 doi: 10.7554/eLife.60312

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
The following previously published data sets were used

Article and author information

Author details

  1. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6378-295X
  2. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1891-9563
  3. Erez Lieberman-Aiden

    Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Peter G Wolynes

    Center for Theoretical Biological Physics, Rice University, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. 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.
  6. 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.
    ORCID icon "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.

Reviewing Editor

  1. Yibing Shan, DE Shaw Research, United States

Publication history

  1. Received: June 22, 2020
  2. Accepted: October 8, 2020
  3. Accepted Manuscript published: October 13, 2020 (version 1)
  4. 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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