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Title: Tension-dependent free energies of nucleosome unwrapping

Abstract

Here, nucleosomes form the basic unit of compaction within eukaryotic genomes, and their locations represent an important, yet poorly understood, mechanism of genetic regulation. Quantifying the strength of interactions within the nucleosome is a central problem in biophysics and is critical to understanding how nucleosome positions influence gene expression. By comparing to single-molecule experiments, we demonstrate that a coarse-grained molecular model of the nucleosome can reproduce key aspects of nucleosome unwrapping. Using detailed simulations of DNA and histone proteins, we calculate the tension-dependent free energy surface corresponding to the unwrapping process. The model reproduces quantitatively the forces required to unwrap the nucleosome and reveals the role played by electrostatic interactions during this process. We then demonstrate that histone modifications and DNA sequence can have significant effects on the energies of nucleosome formation. Most notably, we show that histone tails contribute asymmetrically to the stability of the outer and inner turn of nucleosomal DNA and that depending on which histone tails are modified, the tension-dependent response is modulated differently.

Authors:
 [1];  [1];  [2];  [3]
  1. Univ. of Chicago, Chicago, IL (United States)
  2. Univ. of Wisconsin-Madison, Madison, WI (United States)
  3. Univ. of Chicago, Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Materials Sciences and Engineering Division; US Department of Commerce; National Institute of Standards and Technology (NIST); National Institutes of Health (NIH) - National Human Genome Research Institute (NHGRI)
OSTI Identifier:
1332925
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Accepted Manuscript
Journal Name:
ACS Central Science
Additional Journal Information:
Journal Volume: 2; Journal Issue: 9; Journal ID: ISSN 2374-7943
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Lequieu, Joshua, Cordoba, Andres, Schwartz, David C., and de Pablo, Juan J. Tension-dependent free energies of nucleosome unwrapping. United States: N. p., 2016. Web. doi:10.1021/acscentsci.6b00201.
Lequieu, Joshua, Cordoba, Andres, Schwartz, David C., & de Pablo, Juan J. Tension-dependent free energies of nucleosome unwrapping. United States. doi:10.1021/acscentsci.6b00201.
Lequieu, Joshua, Cordoba, Andres, Schwartz, David C., and de Pablo, Juan J. Tue . "Tension-dependent free energies of nucleosome unwrapping". United States. doi:10.1021/acscentsci.6b00201. https://www.osti.gov/servlets/purl/1332925.
@article{osti_1332925,
title = {Tension-dependent free energies of nucleosome unwrapping},
author = {Lequieu, Joshua and Cordoba, Andres and Schwartz, David C. and de Pablo, Juan J.},
abstractNote = {Here, nucleosomes form the basic unit of compaction within eukaryotic genomes, and their locations represent an important, yet poorly understood, mechanism of genetic regulation. Quantifying the strength of interactions within the nucleosome is a central problem in biophysics and is critical to understanding how nucleosome positions influence gene expression. By comparing to single-molecule experiments, we demonstrate that a coarse-grained molecular model of the nucleosome can reproduce key aspects of nucleosome unwrapping. Using detailed simulations of DNA and histone proteins, we calculate the tension-dependent free energy surface corresponding to the unwrapping process. The model reproduces quantitatively the forces required to unwrap the nucleosome and reveals the role played by electrostatic interactions during this process. We then demonstrate that histone modifications and DNA sequence can have significant effects on the energies of nucleosome formation. Most notably, we show that histone tails contribute asymmetrically to the stability of the outer and inner turn of nucleosomal DNA and that depending on which histone tails are modified, the tension-dependent response is modulated differently.},
doi = {10.1021/acscentsci.6b00201},
journal = {ACS Central Science},
number = 9,
volume = 2,
place = {United States},
year = {2016},
month = {8}
}

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Works referencing / citing this record:

Critical role of histone tail entropy in nucleosome unwinding
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  • The Journal of Chemical Physics, Vol. 150, Issue 18
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Polymer physics across scales: Modeling the multiscale behavior of functional soft materials and biological systems
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  • Spakowitz, Andrew J.
  • The Journal of Chemical Physics, Vol. 151, Issue 23
  • DOI: 10.1063/1.5126852

In silico evidence for sequence-dependent nucleosome sliding
journal, October 2017

  • Lequieu, Joshua; Schwartz, David C.; de Pablo, Juan J.
  • Proceedings of the National Academy of Sciences, Vol. 114, Issue 44
  • DOI: 10.1073/pnas.1705685114

DNA sliding in nucleosomes via twist defect propagation revealed by molecular simulations
journal, February 2018

  • Brandani, Giovanni B.; Niina, Toru; Tan, Cheng
  • Nucleic Acids Research, Vol. 46, Issue 6
  • DOI: 10.1093/nar/gky158

Designing nucleosomal force sensors
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