We theoretically investigate how the intranuclear environment influences the charge of a nucleosome core particle (NCP)—the fundamental unit of chromatin consisting of DNA wrapped around a core of histone proteins. The molecular-based theory explicitly considers the size, shape, conformation, charge, and chemical state of all molecular species—thereby linking the structural state with the chemical/charged state of the system. We investigate how variations in monovalent and divalent salt concentrations, as well as pH, affect the charge distribution across different regions of an NCP and quantify the impact of charge regulation. The effective charge of an NCP emerges from a delicate and complex balance involving the chemical dissociation equilibrium of the amino acids and the DNA-phosphates, the electrostatic interaction between them, and the translational entropy of the mobile solution ions, i.e., counter ion release and ion condensation. From our results, we note the significant effect of divalent magnesium ions on the charge and electrostatic energy as well as the counterion cloud that surrounds an NCP. As a function of magnesium concentration, charge neutralization, and even charge inversion is predicted—in line with experimental observation of NCPs. The strong Mg-dependence of the nucleosome charge state arises from ion bridges between two DNA-phosphates and one ion. We demonstrate that to describe and predict the charged state of an NCP properly, it is essential to consider molecular details, such as DNA-phosphate ion condensation and the acid–base equilibrium of the amino acids that comprise the core histone proteins.
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21 December 2024
Research Article|
December 20 2024
The impact of charge regulation and ionic intranuclear environment on the nucleosome core particle

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Chromatin Structure and Dynamics: Recent Advancements
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Rikkert J. Nap
;
Rikkert J. Nap
(Conceptualization, Data curation, Investigation, Methodology, Software, Validation, Visualization, Writing – original draft, Writing – review & editing)
1
Department of Biomedical Engineering, Northwestern University
, Evanston, Illinois 60208, USA
2
Chemistry of Life Processes Institute, Northwestern University
, Evanston, Illinois 60208, USA
3
Center for Physical Genomics and Engineering, McCormick School of Engineering, Northwestern University
, Evanston, Illinois 60208, USA
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Paola Carillo Gonzalez
;
Paola Carillo Gonzalez
(Data curation, Formal analysis, Investigation, Methodology, Software, Validation, Visualization, Writing – original draft, Writing – review & editing)
1
Department of Biomedical Engineering, Northwestern University
, Evanston, Illinois 60208, USA
2
Chemistry of Life Processes Institute, Northwestern University
, Evanston, Illinois 60208, USA
3
Center for Physical Genomics and Engineering, McCormick School of Engineering, Northwestern University
, Evanston, Illinois 60208, USA
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Aria E. Coraor
;
Aria E. Coraor
(Data curation, Investigation, Methodology, Software, Validation, Visualization, Writing – review & editing)
4
Pritzker School of Molecular Engineering, University of Chicago
, Chicago, Illinois 60637, USA
5
Chan Zuckerberg Biohub Chicago
, Chicago, Illinois 60642, USA
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Ranya K. A. Virk
;
Ranya K. A. Virk
(Conceptualization, Investigation, Methodology, Software, Writing – review & editing)
6
Department of Pharmaceutical Chemistry, University of California
, San Francisco, California 94158, USA
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Juan J. de Pablo
;
Juan J. de Pablo
(Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Supervision, Writing – review & editing)
4
Pritzker School of Molecular Engineering, University of Chicago
, Chicago, Illinois 60637, USA
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Vadim Backman
;
Vadim Backman
(Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Supervision, Writing – review & editing)
1
Department of Biomedical Engineering, Northwestern University
, Evanston, Illinois 60208, USA
2
Chemistry of Life Processes Institute, Northwestern University
, Evanston, Illinois 60208, USA
3
Center for Physical Genomics and Engineering, McCormick School of Engineering, Northwestern University
, Evanston, Illinois 60208, USA
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Igal Szleifer
Igal Szleifer
a)
(Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Supervision, Writing – review & editing)
1
Department of Biomedical Engineering, Northwestern University
, Evanston, Illinois 60208, USA
2
Chemistry of Life Processes Institute, Northwestern University
, Evanston, Illinois 60208, USA
3
Center for Physical Genomics and Engineering, McCormick School of Engineering, Northwestern University
, Evanston, Illinois 60208, USA
7
Department of Chemistry, Northwestern University
, Evanston, Illinois 60208, USA
a)Author to whom correspondence should be addressed: [email protected]
Search for other works by this author on:
Rikkert J. Nap
1,2,3
Paola Carillo Gonzalez
1,2,3
Aria E. Coraor
4,5
Ranya K. A. Virk
6
Juan J. de Pablo
4
Vadim Backman
1,2,3
Igal Szleifer
1,2,3,7,a)
1
Department of Biomedical Engineering, Northwestern University
, Evanston, Illinois 60208, USA
2
Chemistry of Life Processes Institute, Northwestern University
, Evanston, Illinois 60208, USA
3
Center for Physical Genomics and Engineering, McCormick School of Engineering, Northwestern University
, Evanston, Illinois 60208, USA
4
Pritzker School of Molecular Engineering, University of Chicago
, Chicago, Illinois 60637, USA
5
Chan Zuckerberg Biohub Chicago
, Chicago, Illinois 60642, USA
6
Department of Pharmaceutical Chemistry, University of California
, San Francisco, California 94158, USA
7
Department of Chemistry, Northwestern University
, Evanston, Illinois 60208, USA
a)Author to whom correspondence should be addressed: [email protected]
J. Chem. Phys. 161, 235101 (2024)
Article history
Received:
September 30 2024
Accepted:
November 13 2024
Connected Content
A companion article has been published:
Predicting charge of a nucleosome core particle based on its environment
Citation
Rikkert J. Nap, Paola Carillo Gonzalez, Aria E. Coraor, Ranya K. A. Virk, Juan J. de Pablo, Vadim Backman, Igal Szleifer; The impact of charge regulation and ionic intranuclear environment on the nucleosome core particle. J. Chem. Phys. 21 December 2024; 161 (23): 235101. https://doi.org/10.1063/5.0241529
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