Robert Schöpflin

Stralsund University of Applied Science, Stralsund, Mecklenburg-Vorpommern, Germany

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Publications (12)47.41 Total impact

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    ABSTRACT: Chromatin conformation is dynamic and heterogeneous with respect to nucleosome positions, which can be changed by chromatin remodeling complexes in the cell. These molecular machines hydrolyze ATP to translocate or evict nucleosomes, and establish loci with regularly and more irregularly spaced nucleosomes as well as nucleosome-depleted regions. The impact of nucleosome repositioning on the three-dimensional chromatin structure is only poorly understood. Here, we address this issue by using a coarse-grained computer model of arrays of 101 nucleosomes considering several chromatin fiber models with and without linker histones, respectively. We investigated the folding of the chain in dependence of the position of the central nucleosome by changing the length of the adjacent linker DNA in basepair steps. We found in our simulations that these translocations had a strong effect on the shape and properties of chromatin fibers: i), Fiber curvature and flexibility at the center were largely increased and long-range contacts between distant nucleosomes on the chain were promoted. ii), The highest destabilization of the fiber conformation occurred for a nucleosome shifted by two basepairs from regular spacing, whereas effects of linker DNA changes of ∼10 bp in phase with the helical twist of DNA were minimal. iii), A fiber conformation can stabilize a regular spacing of nucleosomes inasmuch as favorable stacking interactions between nucleosomes are facilitated. This can oppose nucleosome translocations and increase the energetic costs for chromatin remodeling. Our computational modeling framework makes it possible to describe the conformational heterogeneity of chromatin in terms of nucleosome positions, and thus advances theoretical models toward a better understanding of how genome compaction and access are regulated within the cell.
    Biophysical Journal 11/2014; 107(9). DOI:10.1016/j.bpj.2014.09.026 · 3.83 Impact Factor
  • Biophysical Journal 01/2014; 106(2):76a. DOI:10.1016/j.bpj.2013.11.495 · 3.83 Impact Factor
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    ABSTRACT: Recent experimental advancements allow determining positions of nucleosomes for complete genomes. However, the resulting nucleosome occupancy maps are averages of heterogeneous cell populations. Accordingly, they represent a snapshot of a dynamic ensemble at a single time point with an overlay of many configurations from different cells. To study the organization of nucleosomes along the genome and to understand the mechanisms of nucleosome translocation, it is necessary to retrieve features of specific conformations from the population average. Here, we present a method for identifying non-overlapping nucleosome configurations that combines binary-variable analysis and a Monte Carlo approach with a simulated annealing scheme. In this manner we obtain specific nucleosome configurations and optimized solutions for the complex positioning patterns from experimental data. We apply the method to compare nucleosome positioning at transcription factor binding sites in different mouse cell types. Our method can model nucleosome translocations at regulatory genomic elements and generate configurations for simulations of the spatial folding of the nucleosome chain. Source code, precompiled binaries, test data and a web-based test installation are freely available at, SUPPLEMENTARY INFORMATION: Supplementary figures and tables are available at Bioinformatics online.
    Bioinformatics 07/2013; 29(19). DOI:10.1093/bioinformatics/btt404 · 4.62 Impact Factor
  • Biophysical Journal 01/2013; 104(2):581-. DOI:10.1016/j.bpj.2012.11.3227 · 3.83 Impact Factor
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    ABSTRACT: A completely new crystal-growth device has been developed that permits charting a course across the phase diagram to produce crystalline samples optimized for diffraction experiments. The utility of the device is demonstrated for the production of crystals for the traditional X-ray diffraction data-collection experiment, of microcrystals optimal for data-collection experiments at a modern microbeam insertion-device synchrotron beamline and of nanocrystals required for data collection on an X-ray laser beamline.
    Acta Crystallographica Section F Structural Biology and Crystallization Communications 08/2012; 68(Pt 8):994-8. DOI:10.1107/S1744309112024074 · 0.57 Impact Factor
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    ABSTRACT: The wormlike-chain (WLC) model is widely used to describe the energetics of DNA bending. Motivated by recent experiments, alternative, so-called subelastic chain models were proposed that predict a lower elastic energy of highly bent DNA conformations. Until now, no unambiguous verification of these models has been obtained because probing the elasticity of DNA on short length scales remains challenging. Here we investigate the limits of the WLC model using coarse-grained Monte Carlo simulations to model the supercoiling of linear DNA molecules under tension. At a critical supercoiling density, the DNA extension decreases abruptly due to the sudden formation of a plectonemic structure. This buckling transition is caused by the large energy required to form the tightly bent end-loop of the plectoneme and should therefore provide a sensitive benchmark for model evaluation. Although simulations based on the WLC energetics could quantitatively reproduce the buckling measured in magnetic tweezers experiments, the buckling almost disappears for the tested linear subelastic chain model. Thus, our data support the validity of a harmonic bending potential even for small bending radii down to 3.5 nm.
    Biophysical Journal 07/2012; 103(2):323-30. DOI:10.1016/j.bpj.2012.05.050 · 3.83 Impact Factor
  • Biophysical Journal 01/2012; 102(3):482-. DOI:10.1016/j.bpj.2011.11.2643 · 3.83 Impact Factor
  • Biophysical Journal 01/2012; 102(3):275-. DOI:10.1016/j.bpj.2011.11.1517 · 3.83 Impact Factor
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    ABSTRACT: DNA-DNA interactions are important for genome compaction and transcription regulation. In studies of such complex processes, DNA is often modeled as a homogeneously charged cylinder and its electrostatic interactions are calculated within the framework of the Poisson-Boltzmann equation. Commonly, a charge adaptation factor is used to address limitations of this theoretical approach. Despite considerable theoretical and experimental efforts, a rigorous quantitative assessment of this parameter is lacking. Here, we comprehensively characterized DNA-DNA interactions in the presence of monovalent ions by analyzing the supercoiling behavior of single DNA molecules held under constant tension. Both a theoretical model and coarse-grained simulations of this process revealed a surprisingly small effective DNA charge of 40% of the nominal charge density, which was additionally supported by all-atom molecular dynamics simulations.
    Physical Review Letters 10/2010; 105(15):158101. DOI:10.1103/PhysRevLett.105.158101 · 7.73 Impact Factor
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    ABSTRACT: The three-dimensional structure of chromatin affects DNA accessibility and is therefore a key regulator of gene expression. However, the path of the DNA between consecutive nucleosomes, and the resulting chromatin fiber organization remain controversial. The conformational space available for the folding of the nucleosome chain has been analytically described by phase diagrams with a two-angle model, which describes the chain trajectory by a DNA entry-exit angle at the nucleosome and a torsion angle between consecutive nucleosomes. Here, a novel type of numerical phase diagrams is introduced that relates the geometric phase space to the energy associated with a given chromatin conformation. The resulting phase diagrams revealed differences in the energy landscape that reflect the probability of a given conformation to form in thermal equilibrium. Furthermore, we investigated the effects of entropy and additional degrees of freedom in the dynamic phase diagrams by performing Monte Carlo simulations of the initial chain trajectories. Using our approach, we were able to demonstrate that conformations that initially were geometrically impossible could evolve into energetically favorable states in thermal equilibrium due to DNA bending and torsion. In addition, dynamic phase diagrams were applied to identify chromatin fibers that reflect certain experimentally determined features.
    Biophysical Journal 03/2010; 98(6):1028-37. DOI:10.1016/j.bpj.2009.11.040 · 3.83 Impact Factor
  • Biophysical Journal 01/2010; 98(3):470-. DOI:10.1016/j.bpj.2009.12.2556 · 3.83 Impact Factor
  • Biophysical Journal 01/2010; 98(3). DOI:10.1016/j.bpj.2009.12.2555 · 3.83 Impact Factor

Publication Stats

83 Citations
47.41 Total Impact Points


  • 2010–2014
    • Stralsund University of Applied Science
      Stralsund, Mecklenburg-Vorpommern, Germany
    • Technische Universität Dresden
      Dresden, Saxony, Germany