Abstract

Stochastic single particle trajectories are used to explore the local chromatin organization. We present here a statistical analysis of the first contact time distributions between two tagged loci recorded experimentally. First, we extract the association and dissociation times from data for various genomic distances between loci, and we show that the looping time occurs in confined nanometer regions. Second, we characterize the looping time distribution for two loci in the presence of multiple DNA damages. Finally, we construct a polymer model, that accounts for the local chromatin organization before and after a double-stranded DNA break (DSB), to estimate the level of chromatin decompaction. This novel passage time statistics method allows extracting transient dynamic at scales varying from one to few hundreds of nanometers, it predicts the local changes in the number of binding molecules following DSB and can be used to characterize the local dynamic of the chromatin.

Highlights

  • Analysis of recent single particle trajectories (SPTs) of a tagged single locus revealed that chromatin dynamics is mostly driven by stochastic forces[1, 2]

  • The construction of the present statistical method is based on the first passage time for two loci entering and exiting a small ball of radius ε

  • Using an exponential fit to the data for all strains of length Δ, we find that the mean first passage time (FET) (MFET) slightly decreases from 3.2 s for Δ = 25 kbp to 2 s for Δ = 108 kbp (Fig. 2A blue circles)

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Summary

Introduction

Analysis of recent single particle trajectories (SPTs) of a tagged single locus revealed that chromatin dynamics is mostly driven by stochastic forces[1, 2]. The extracted statistical parameters are the diffusion coefficient, local tethering forces, the radius of gyration, radius of confinement[1, 2], and the distribution of anomalous exponents of tagged loci along the chromatin, which characterizes the deviation of their dynamics from pure diffusion[4, 20]. We explore the chromatin state from the transient statistics of recurrent visits of two tagged loci This approach is new and is not contained in other work involving two spots trajectories, which use equilibrium thermodynamic models for steady-state encounter frequency[21] or specific chromatin arrangement[22]. The statistics of FDT and FET is not contained in moments associated with each locus separately, but revealed by their correlated motion

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