Explicit Ion Modeling Predicts Physicochemical Interactions for Chromatin Organization DOI Creative Commons
Xingcheng Lin, Bin Zhang

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 18, 2023

Abstract Molecular mechanisms that dictate chromatin organization in vivo are under active investigation, and the extent to which intrinsic interactions contribute this process remains debatable. A central quantity for evaluating their contribution is strength of nucleosome-nucleosome binding, previous experiments have estimated range from 2 14 k B T . We introduce an explicit ion model dramatically enhance accuracy residue-level coarse-grained modeling approaches across a wide ionic concentrations. This allows de novo predictions computationally efficient, enabling large-scale conformational sampling free energy calculations. It reproduces energetics protein-DNA binding unwinding single nucleosomal DNA, resolves differential impact mono divalent ions on conformations. Moreover, we showed can reconcile various quantifying interactions, providing explanation large discrepancy between existing estimations. predict interaction at physiological conditions be 9 , value nonetheless sensitive DNA linker length presence histones. Our study strongly supports physicochemical phase behavior aggregates inside nucleus.

Language: Английский

On the stability and layered organization of protein-DNA condensates DOI
Andrew P. Latham, Bin Zhang

Biophysical Journal, Journal Year: 2022, Volume and Issue: 121(9), P. 1727 - 1737

Published: March 29, 2022

Language: Английский

Citations

40
Computational methods for analysing multiscale 3D genome organization DOI
Yang Zhang, Lorenzo Boninsegna, Muyu Yang

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(2), P. 123 - 141

Published: Sept. 6, 2023

Language: Английский

Citations

37
From Nucleosomes to Compartments: Physicochemical Interactions Underlying Chromatin Organization DOI
Shuming Liu, Advait Athreya,

Zhuohan Lao

et al.

Annual Review of Biophysics, Journal Year: 2024, Volume and Issue: 53(1), P. 221 - 245

Published: Feb. 12, 2024

Chromatin organization plays a critical role in cellular function by regulating access to genetic information. However, understanding chromatin folding is challenging due its complex, multiscale nature. Significant progress has been made studying vitro systems, uncovering the structure of individual nucleosomes and their arrays, elucidating physicochemical forces stabilizing these structures. Additionally, remarkable advancements have achieved characterizing vivo, particularly at whole-chromosome level, revealing important features such as loops, topologically associating domains, nuclear compartments. bridging gap between vivo studies remains challenging. The resemblance conformations relevance internucleosomal interactions for are subjects debate. This article reviews experimental computational conducted various length scales, highlighting significance intrinsic roles vivo.

Language: Английский

Citations

15
Chromatin phase separation and nuclear shape fluctuations are correlated in a polymer model of the nucleus DOI Creative Commons
Ali Goktug Attar, Jarosław Paturej, Edward J. Banigan

et al.

Nucleus, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 16, 2024

Abnormal cell nuclear shapes are hallmarks of diseases, including progeria, muscular dystrophy, and many cancers. Experiments have shown that disruption heterochromatin increases in euchromatin lead to deformations, such as blebs ruptures. However, the physical mechanisms through which chromatin governs shape poorly understood. To investigate how might govern morphology, we studied microphase separation a composite coarse-grained polymer elastic shell simulation model. By varying density, composition, heterochromatin-lamina interactions, show phase organization may perturb shape. Increasing density stabilizes lamina against large fluctuations. increasing levels or interactions enhances fluctuations by "wetting"-like interaction. In contrast, insensitive heterochromatin's internal structure. Our simulations suggest peripheral accumulation could while stabilization likely occurs other than organization.

Language: Английский

Citations

9
Phase Separation and Correlated Motions in Motorized Genome DOI
Zhongling Jiang, Yifeng Qi, Kartik Kamat

et al.

The Journal of Physical Chemistry B, Journal Year: 2022, Volume and Issue: 126(30), P. 5619 - 5628

Published: July 20, 2022

The human genome is arranged in the cell nucleus nonrandomly, and phase separation has been proposed as an important driving force for organization. However, active system, contribution of nonequilibrium activities to structure dynamics remains be explored. We simulated using energy function parametrized with chromosome conformation capture (Hi-C) data presence active, nondirectional forces that break detailed balance. found may arise from transcription chromatin remodeling can dramatically impact spatial localization heterochromatin. When applied euchromatin, drive heterochromatin nuclear envelope compete passive interactions among tend pull them opposite directions. Furthermore, induce long-range correlations genomic loci beyond single territories. further showed could understood effective temperature defined fluctuation-dissipation ratio. Our study suggests significantly dynamics, producing unexpected collective phenomena.

Language: Английский

Citations

29
Explicit ion modeling predicts physicochemical interactions for chromatin organization DOI Creative Commons
Xingcheng Lin, Bin Zhang

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Aug. 21, 2023

Molecular mechanisms that dictate chromatin organization in vivo are under active investigation, and the extent to which intrinsic interactions contribute this process remains debatable. A central quantity for evaluating their contribution is strength of nucleosome-nucleosome binding, previous experiments have estimated range from 2 14 k B T . We introduce an explicit ion model dramatically enhance accuracy residue-level coarse-grained modeling approaches across a wide ionic concentrations. This allows de novo predictions computationally efficient, enabling large-scale conformational sampling free energy calculations. It reproduces energetics protein-DNA binding unwinding single nucleosomal DNA, resolves differential impact mono- divalent ions on conformations. Moreover, we showed can reconcile various quantifying interactions, providing explanation large discrepancy between existing estimations. predict interaction at physiological conditions be 9 , value nonetheless sensitive DNA linker length presence histones. Our study strongly supports physicochemical phase behavior aggregates inside nucleus.

Language: Английский

Citations

16
Nuclear speckle biology: At the cross-roads of discovery and functional analysis DOI Creative Commons
Pankaj Chaturvedi, Andrew S. Belmont

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 91, P. 102438 - 102438

Published: Sept. 27, 2024

Language: Английский

Citations

4
Efficient Hi-C inversion facilitates chromatin folding mechanism discovery and structure prediction DOI Creative Commons
Greg Schuette, Xinqiang Ding, Bin Zhang

et al.

Biophysical Journal, Journal Year: 2023, Volume and Issue: 122(17), P. 3425 - 3438

Published: July 26, 2023

Language: Английский

Citations

10
OpenABC enables flexible, simplified, and efficient GPU accelerated simulations of biomolecular condensates DOI Creative Commons
Shuming Liu, Cong Wang, Andrew P. Latham

et al.

PLoS Computational Biology, Journal Year: 2023, Volume and Issue: 19(9), P. e1011442 - e1011442

Published: Sept. 11, 2023

Biomolecular condensates are important structures in various cellular processes but challenging to study using traditional experimental techniques. In silico simulations with residue-level coarse-grained models strike a balance between computational efficiency and chemical accuracy. They could offer valuable insights by connecting the emergent properties of these complex systems molecular sequences. However, existing often lack easy-to-follow tutorials implemented software that is not optimal for condensate simulations. To address issues, we introduce OpenABC, package greatly simplifies setup execution multiple force fields Python scripting. OpenABC seamlessly integrates OpenMM dynamics engine, enabling efficient performance on single GPU rivals speed achieved hundreds CPUs. We also provide tools convert configurations all-atom atomistic anticipate will significantly facilitate adoption broader community investigate structural dynamical condensates.

Language: Английский

Citations

10
Explicit ion modeling predicts physicochemical interactions for chromatin organization DOI Creative Commons
Xingcheng Lin, Bin Zhang

eLife, Journal Year: 2024, Volume and Issue: 12

Published: Jan. 30, 2024

Molecular mechanisms that dictate chromatin organization in vivo are under active investigation, and the extent to which intrinsic interactions contribute this process remains debatable. A central quantity for evaluating their contribution is strength of nucleosome-nucleosome binding, previous experiments have estimated range from 2 14 k B T . We introduce an explicit ion model dramatically enhance accuracy residue-level coarse-grained modeling approaches across a wide ionic concentrations. This allows de novo predictions computationally efficient, enabling large-scale conformational sampling free energy calculations. It reproduces energetics protein-DNA binding unwinding single nucleosomal DNA, resolves differential impact mono- divalent ions on conformations. Moreover, we showed can reconcile various quantifying interactions, providing explanation large discrepancy between existing estimations. predict interaction at physiological conditions be 9 , value nonetheless sensitive DNA linker length presence histones. Our study strongly supports physicochemical phase behavior aggregates inside nucleus.

Language: Английский

Citations

3