How does torsional rigidity affect the wrapping transition of a semiflexible chain around a spherical core?

We investigated the effect of torsional rigidity of a semiflexible chain on the wrapping transition around a spherical core, as a model of nucleosome, the fundamental unit of chromatin. Through molecular dynamics simulation, we show that the torsional effect has a crucial effect on the chain wrapping around the core under the topological constraints. In particular, the torsional stress (i) induces the wrapping/unwrapping transition, and (ii) leads to a unique complex structure with an antagonistic wrapping direction which never appears without the topological constraints. We further examine the effect of the stretching stress for the nucleosome model, in relation to the unique characteristic effect of the torsional stress on the manner of wrapping

Unwrapping of DNA-protein complexes under external stretching

A DNA-protein complex modelled by a semiflexible chain and an attractive spherical core is studied in the situation when an external stretching force is acting on one end monomer of the chain while the other end monomer is kept fixed in space. Without stretching force, the chain is wrapped around the core. By applying an external stretching force, unwrapping of the complex is induced. We study the statics and the dynamics of the unwrapping process by computer simulation and simple phenomenological theory. We find two different scenarios depending on the chain stiffness: For a flexible chain, the extension of the complex scales linearly with the external force applied. The sphere-chain complex is disordered, i.e. there is no clear winding of the chain around the sphere. For a stiff chain, on the other hand, the complex structure is ordered, which is reminiscent to nucleosome. There is a clear winding number and the unwrapping process under external stretching is discontinuous with jumps of the distance-force curve. This is associated to discrete unwinding processes of the complex. Our predictions are of relevance for experiments, which measure force-extension curves of DNA-protein complexes, such as nucleosome, using optical tweezers.Comment: 8 pages, 7 figure

All-or-none switching of transcriptional activity on single DNA molecules caused by a discrete conformational transition

Recently, it has been confirmed that long duplex DNA molecules with sizes larger than several tens of kilo-base pairs (kbp), exhibit a discrete conformational transition from an elongated coil state to a compact globule state upon the addition of various kinds of chemical species that usually induce DNA condensation. In this study, we performed a single-molecule observation on a large DNA, Lambda ZAP II DNA (ca. 41 kbp), in a solution containing RNA polymerase and substrates along with spermine, a tetravalent cation, at different concentrations, by use of fluorescence staining of both DNA and RNA. We found that transcription, or RNA production, is completely inhibited in the compact state, but is actively performed in the unfolded coil state. Such an all-or-none effect on transcriptional activity induced by the discrete conformational transition of single DNA molecules is discussed in relation to the mechanism of the regulation of large-scale genetic activity.Comment: 14 pages, 2 figure

Orientational correlations in confined DNA

We study how the orientational correlations of DNA confined to nanochannels depend on the channel diameter D by means of Monte Carlo simulations and a mean-field theory. This theory describes DNA conformations in the experimentally relevant regime where the Flory-de Gennes theory does not apply. We show how local correlations determine the dependence of the end-to-end distance of the DNA molecule upon D. Tapered nanochannels provide the necessary resolution in D to study experimentally how the extension of confined DNA molecules depends upon D. Our experimental and theoretical results are in qualitative agreement.Comment: Revised version including supplemental material, 7 pages, 8 figure

Chromatin: a tunable spring at work inside chromosomes

This paper focuses on mechanical aspects of chromatin biological functioning. Within a basic geometric modeling of the chromatin assembly, we give for the first time the complete set of elastic constants (twist and bend persistence lengths, stretch modulus and twist-stretch coupling constant) of the so-called 30-nm chromatin fiber, in terms of DNA elastic properties and geometric properties of the fiber assembly. The computation naturally embeds the fiber within a current analytical model known as the ``extensible worm-like rope'', allowing a straightforward prediction of the force-extension curves. We show that these elastic constants are strongly sensitive to the linker length, up to 1 bp, or equivalently to its twist, and might locally reach very low values, yielding a highly flexible and extensible domain in the fiber. In particular, the twist-stretch coupling constant, reflecting the chirality of the chromatin fiber, exhibits steep variations and sign changes when the linker length is varied. We argue that this tunable elasticity might be a key feature for chromatin function, for instance in the initiation and regulation of transcription.Comment: 38 pages 15 figure

Axial turbulent flow in a circular pipe containing a fixed eccentric core

The turbulent flow of air through a circular pipe containing a fixed eccentric core was investigated at one air flow and one fixed eccentricity

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Equation of state for polymer liquid crystals: theory and experiment

The first part of this paper develops a theory for the free energy of lyotropic polymer nematic liquid crystals. We use a continuum model with macroscopic elastic moduli for a polymer nematic phase. By evaluating the partition function, considering only harmonic fluctuations, we derive an expression for the free energy of the system. We find that the configurational entropic part of the free energy enhances the effective repulsive interactions between the chains. This configurational contribution goes as the fourth root of the direct interactions. Enhancement originates from the coupling between bending fluctuations and the compressibility of the nematic array normal to the average director. In the second part of the paper we use osmotic stress to measure the equation of state for DNA liquid crystals in 0.1M to 1M NaCl solutions. These measurements cover 5 orders of magnitude in DNA osmotic pressure. At high osmotic pressures the equation of state, dominated by exponentially decaying hydration repulsion, is independent of the ionic strength. At lower pressures the equation of state is dominated by fluctuation enhanced electrostatic double layer repulsion. The measured equation of state for DNA fits well with our theory for all salt concentrations. We are able to extract the strength of the direct electrostatic double layer repulsion. This is a new and alternative way of measuring effective charge densities along semiflexible polyelectrolytes.Comment: text + 5 figures. Submitted to PR

Cell-Cycle Dependence of Transcription Dominates Noise in Gene Expression

The large variability in mRNA and protein levels found from both static and dynamic measurements in single cells has been largely attributed to random periods of transcription, often occurring in bursts. The cell cycle has a pronounced global role in affecting transcriptional and translational output, but how this influences transcriptional statistics from noisy promoters is unknown and generally ignored by current stochastic models. Here we show that variable transcription from the synthetic tetO promoter in S. cerevisiae is dominated by its dependence on the cell cycle. Real-time measurements of fluorescent protein at high expression levels indicate tetO promoters increase transcription rate ~2-fold in S/G2/M similar to constitutive genes. At low expression levels, where tetO promoters are thought to generate infrequent bursts of transcription, we observe random pulses of expression restricted to S/G2/M, which are correlated between homologous promoters present in the same cell. The analysis of static, single-cell mRNA measurements at different points along the cell cycle corroborates these findings. Our results demonstrate that highly variable mRNA distributions in yeast are not solely the result of randomly switching between periods of active and inactive gene expression, but instead largely driven by differences in transcriptional activity between G1 and S/G2/M.GM095733BBBE 103316MIT Startup Fun