Polymer model with long-range interactions: Analysis and applications to the chromatin structure

Amitai, Assaf; Holcman, David

doi:10.1103/physreve.88.052604

Cited by 47 publications

(81 citation statements)

References 25 publications

(33 reference statements)

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“…By definition, 1 < β 2 [12] and the Rouse polymer is recovered for β = 2, for which only nearest neighbors are connected. The model also relates the structure parameter β to the subdiffusive dynamics of a tagged monomer by the relation α = 1 − 1/β.…”

Section: Following Polymer Decompaction the Local Search Time Decmentioning

confidence: 99%

“…However, it is not clear how these times contribute to the mean encounter time for two monomers located on two different polymers. In addition, in a confined environment, the probability distribution function of monomers varies along the polymer chain [11,12], which again can influence the search time.To account for chromatin reorganization following DSB [4], we study here the random search of two monomers that belongs to two different monomers using the Rouse model [13] and the β-polymer [12]. Other polymer models of chromatin could be used for stochastic simulations, but deriving asymptotic laws remains difficult for them [4,[14][15][16] because they account for many physical forces.…”

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confidence: 99%

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confidence: 99%

“…Following break induction, the anomalous exponent α increases [4], reflecting also an increase in mobility and a local chromatin decondensation. These modifications can be accounted for by using the β model [12], which is a coarsegrained polymer model of chromatin that takes into account far away chromatin interactions. Long-range interactions could be mediated by protein-protein interactions, such as cohesin and condensin.…”

mentioning

confidence: 99%

“…To account for chromatin reorganization following DSB [4], we study here the random search of two monomers that belongs to two different monomers using the Rouse model [13] and the β-polymer [12]. Other polymer models of chromatin could be used for stochastic simulations, but deriving asymptotic laws remains difficult for them [4,[14][15][16] because they account for many physical forces.…”

mentioning

confidence: 99%

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Encounter times of chromatin loci influenced by polymer decondensation

Amitai

Holcman

2018

Phys. Rev. E

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The time for a DNA sequence to find its homologous counterpart depends on a long random search inside the cell nucleus. Using polymer models, we compute here the mean first encounter time (MFET) between two sites located on two different polymer chains and confined locally by potential wells. We find that reducing tethering forces acting on the polymers results in local decondensation, and numerical simulations of the polymer model show that these changes are associated with a reduction of the MFET by several orders of magnitude. We derive here new asymptotic formula for the MFET, confirmed by Brownian simulations. We conclude from the present modeling approach that the fast search for homology is mediated by a local chromatin decondensation due to the release of multiple chromatin tethering forces. The present scenario could explain how the homologous recombination pathway for double-stranded DNA repair is controlled by its random search step. DOI: 10.1103/PhysRevE.97.032417 Repairing DNA double-strand breaks (DSBs) is a key step for cell survival. However, the underlying physical mechanism remains difficult to describe, mostly because it involves multiple molecular steps involving small (nanometer) and large (micrometer) scales. During the homologous recombination (HR) pathway, broken strands perform inside a large portion of the cell nucleus a random search for a homologous DNA template. Once this template is found, it will be used to copy the missing base pairs before repair [1]. As revealed by single-particle trajectories of chromatin [2,3], following a DSB, the broken locus dynamics is modified so that it can scan a larger area of the nucleus. This modification was attributed in part to chromatin decondensation and the release of tethering forces acting locally on the chromatin [4]. These changes could have consequences on the search for a homologous template. We present here polymer modeling and analytical tools to further characterize this search step.We recall that search processes involving two loci located on the same polymers have been investigated in the context of polymer looping [5][6][7][8]. However, much less is known about the mean time for two monomers belonging to two different polymers. The multiple relaxation times associated with the polymer dynamics [9] shows that computing the looping time cannot be obtained by the classical activation escape from a potential well (representing the end-to-end distance energy) [10]. For a long polymer, the mean encounter time is influenced by the slowest internal relaxation times of the polymer [9]. However, it is not clear how these times contribute to the mean encounter time for two monomers located on two different polymers. In addition, in a confined environment, the probability distribution function of monomers varies along the polymer chain [11,12], which again can influence the search time.To account for chromatin reorganization following DSB [4], we study here the random search of two monomers that belongs to two different monomers using the Ro...

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Section: Following Polymer Decompaction the Local Search Time Decmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Encounter times of chromatin loci influenced by polymer decondensation

Amitai

Holcman

2018

Phys. Rev. E

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A guide for single‐particle chromatin tracking in live cell nuclei

Zhang

Seitz

Chang

et al. 2022

Cell Biology International

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The emergence of labeling strategies and live cell imaging methods enables the imaging of chromatin in living cells at single digit nanometer resolution as well as milliseconds temporal resolution. These technical breakthroughs revolutionize our understanding of chromatin structure, dynamics and functions. Single molecule tracking algorithms are usually preferred to quantify the movement of these intranucleus elements to interpret the spatiotemporal evolution of the chromatin. In this review, we will first summarize the fluorescent labeling strategy of chromatin in live cells which will be followed by a systematic comparison of live cell imaging instrumentation. With the proper microscope, we will discuss the image analysis pipelines to extract the biophysical properties of the chromatin. Finally, we expect to give practical suggestions to broad biologists on how to select methods and link to the model properly according to different investigation purposes.

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Procedures for Model-Guided Data Analysis of Chromosomal Loci Dynamics at Short Time Scales

Lagomarsino

2017

The Bacterial Nucleoid

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Polymer model with long-range interactions: Analysis and applications to the chromatin structure

Cited by 47 publications

References 25 publications

Encounter times of chromatin loci influenced by polymer decondensation

Encounter times of chromatin loci influenced by polymer decondensation

A guide for single‐particle chromatin tracking in live cell nuclei

Procedures for Model-Guided Data Analysis of Chromosomal Loci Dynamics at Short Time Scales

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