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

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Май 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.

Язык: Английский

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

Zhuohan Lao

и другие.

Annual Review of Biophysics, Год журнала: 2024, Номер 53(1), С. 221 - 245

Опубликована: Фев. 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.

Язык: Английский

Процитировано

18
On the stability and layered organization of protein-DNA condensates DOI
Andrew P. Latham, Bin Zhang

Biophysical Journal, Год журнала: 2022, Номер 121(9), С. 1727 - 1737

Опубликована: Март 29, 2022

Язык: Английский

Процитировано

43
Computational methods for analysing multiscale 3D genome organization DOI
Yang Zhang, Lorenzo Boninsegna, Muyu Yang

и другие.

Nature Reviews Genetics, Год журнала: 2023, Номер 25(2), С. 123 - 141

Опубликована: Сен. 6, 2023

Язык: Английский

Процитировано

37
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

и другие.

Nucleus, Год журнала: 2024, Номер 15(1)

Опубликована: Май 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.

Язык: Английский

Процитировано

11
A predictive chromatin architecture nexus regulates transcription and DNA damage repair DOI Creative Commons
Audesh Bhat,

Sonali Bhan,

Aindrila Kabiraj

и другие.

Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 108300 - 108300

Опубликована: Фев. 1, 2025

Genomes are blueprints of life essential for an organism's survival, propagation, and evolutionary adaptation. Eukaryotic genomes comprises DNA, core histones several other nonhistone proteins packaged into chromatin in the tiny nucleus. Chromatin structural organization restricts transcription protein DNA access, permitting binding only after specific remodelling events. The fundamental processes living cells, including transcription, replication, repair, recombination, thus regulated by structure through ATP-dependent remodelling, histone variant incorporation, various covalent modifications phosphorylation, acetylation, ubiquitination. These modifications, particularly involving H2AX, furthermore play crucial roles damage responses enabling repair access to damage. also stabilizes genome regulating mechanisms while suppressing from endogenous exogenous sources. Environmental factors such as ionizing radiations induce damage, if is compromised, can lead chromosomal abnormalities gene amplifications observed tumor types. Consequently architecture controls blueprint fidelity activity: it orchestrates correct expression, genomic integrity, recombination. This review considers connecting functional outcomes impacting integrity emerging grand challenge predictive molecular cell biology.

Язык: Английский

Процитировано

2
Phase Separation and Correlated Motions in Motorized Genome DOI
Zhongling Jiang, Yifeng Qi, Kartik Kamat

и другие.

The Journal of Physical Chemistry B, Год журнала: 2022, Номер 126(30), С. 5619 - 5628

Опубликована: Июль 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.

Язык: Английский

Процитировано

31
Explicit ion modeling predicts physicochemical interactions for chromatin organization DOI Creative Commons
Xingcheng Lin, Bin Zhang

eLife, Год журнала: 2023, Номер 12

Опубликована: Авг. 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.

Язык: Английский

Процитировано

16
Explicit ion modeling predicts physicochemical interactions for chromatin organization DOI Creative Commons
Xingcheng Lin, Bin Zhang

eLife, Год журнала: 2024, Номер 12

Опубликована: Янв. 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.

Язык: Английский

Процитировано

5
OpenABC enables flexible, simplified, and efficient GPU accelerated simulations of biomolecular condensates DOI Creative Commons
Shuming Liu, Cong Wang, Andrew P. Latham

и другие.

PLoS Computational Biology, Год журнала: 2023, Номер 19(9), С. e1011442 - e1011442

Опубликована: Сен. 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.

Язык: Английский

Процитировано

12
Molecular determinants for the layering and coarsening of biological condensates DOI Creative Commons
Andrew P. Latham, Bin Zhang

Aggregate, Год журнала: 2022, Номер 3(6)

Опубликована: Дек. 1, 2022

Abstract Many membraneless organelles, or biological condensates, form through phase separation, and play key roles in signal sensing transcriptional regulation. While the functional importance of these condensates has inspired many studies to characterize their stability spatial organization, underlying principles that dictate emergent properties are still being uncovered. In this review, we examine recent work on especially multicomponent systems. We focus connecting molecular factors such as binding energy, valency, stoichiometry with interfacial tension, explaining nontrivial interior organization condensates. further discuss mechanisms arrest condensate coalescence by lowering surface tension introducing kinetic barriers stabilize multidroplet state.

Язык: Английский

Процитировано

18