Biophysical Perspective: The Latest Twists in Chromatin Remodeling

International audienceIn its most restrictive interpretation, the notion of chromatin remodeling refers to the action of chromatin remodeling enzymes on nucleosomes with the aim to displace and remove them from the chromatin fiber (the effective polymer formed by a DNA molecule and proteins). This local modification of the fiber structure can have consequences for the initiation and repression of the transcription process and, when the remodeling processes spreads along the fiber, also results in long-range effects essential for fiber condensation. There are three regulatory levels of relevance that can be distinguished for this process: the first is the intrinsic sequence preference of the histone octamer which rules the positioning of the nucleosome along the DNA, notably in relation to the genetic information coded in DNA, the second is the recognition or selection of nucleosomal substrates by remodeling complexes, and the final one the motor action on the nucleosome exerted by the chromatin remodeler. On each of these three levels recent work has been able to provide crucial insights which add new twists to this exciting and unfinished story, which we highlight in this perspective

Chromatin remodelers as active Brownian dimers

International audienceChromatin remodelers are molecular motors which actively displace nucleosomes on chromatin. Recent results on the structural properties of these motors indicate that the displacement of nucleosomal DNA corresponds to an inchworm motion induced by the generation and propagation of twist defects. Here we show that this basic action mechanism can be described by a coarse-grained active Brownian dimer (ABD) model, thereby quantitatively rationalizing the notion of inchworm motion. The model allows for extensions to more microscopic as well towards more macroscopic descriptions of chromatin hydrodynamics

Electrostatic complexation of spheres and chains under elastic stress

We consider the complexation of highly charged semiflexible polyelectrolytes with oppositely charged macroions. On the basis of scaling arguments we discuss how the resulting complexes depend on the persistence length of the polyelectrolyte, the salt concentration, and the sizes and charges of the chain and the macroions. We study first the case of complexation with a single sphere and calculate the wrapping length of the chain. We then extend our considerations to complexes involving many wrapped spheres and study cooperative effects. The mechanical properties of such a complex under an external deformation are evaluated.Comment: 16 pages, submitted to J. Chem. Phy

Pioneer transcription factors in chromatin remodeling: the kinetic proofreading view

Pioneer transcription factors are a recently defined class of transcription factors which can bind directly to nucleosomal DNA; they play a key role in gene activation in certain pathways. Here we quantify their role in the initiation of nucleosome displacement within the kinetic proofreading scenario of chromatin remodeling. The model allows one to perform remodeling efficiency comparisons for scenarios involving different types of transcription factors and remodelers as a function of their binding and unbinding rates and concentrations. Our results demonstrate a way to fine-tune the specificity of processes that modify the chromatin structure in transcriptional initiation.Biological and Soft Matter PhysicsTheoretical Physic

Polymer reptation and nucleosome repositioning

We consider how beads can diffuse along a chain that wraps them, without becoming displaced from the chain; our proposed mechanism is analogous to the reptation of "stored length" in more familiar situations of polymer dynamics. The problem arises in the case of globular aggregates of proteins (histones) that are wound by DNA in the chromosomes of plants and animals; these beads (nucleosomes) are multiply wrapped and yet are able to reposition themselves over long distances, while remaining bound by the DNA chain.Comment: 9 pages, including 2 figures, to be published in Phys. Rev. Let

DNA Spools under Tension

DNA-spools, structures in which DNA is wrapped and helically coiled onto itself or onto a protein core are ubiquitous in nature. We develop a general theory describing the non-equilibrium behavior of DNA-spools under linear tension. Two puzzling and seemingly unrelated recent experimental findings, the sudden quantized unwrapping of nucleosomes and that of DNA toroidal condensates under tension are theoretically explained and shown to be of the same origin. The study provides new insights into nucleosome and chromatin fiber stability and dynamics

Conformation of a Polyelectrolyte Complexed to a Like-Charged Colloid

We report results from a molecular dynamics (MD) simulation on the conformations of a long flexible polyelectrolyte complexed to a charged sphere, \textit{both negatively charged}, in the presence of neutralizing counterions in the strong Coulomb coupling regime. The structure of this complex is very sensitive to the charge density of the polyelectrolyte. For a fully charged polyelectrolyte the polymer forms a dense two-dimensional "disk", whereas for a partially charged polyelectrolyte the monomers are spread over the colloidal surface. A mechanism involving the \textit{overcharging} of the polyelectrolyte by counterions is proposed to explain the observed conformations.Comment: 4 pages, 4 figures (6 EPS files

Organized condensation of worm-like chains

We present results relevant to the equilibrium organization of DNA strands of arbitrary length interacting with a spherical organizing center, suggestive of DNA-histone complexation in nucleosomes. We obtain a rich phase diagram in which a wrapping state is transformed into a complex multi-leafed, rosette structure as the adhesion energy is reduced. The statistical mechanics of the "melting" of a rosette can be mapped into an exactly soluble one-dimensional many-body problem.Comment: 15 pages, 2 figures in a pdf fil

Kinetic control of nucleosome displacement by ISWI/ACF chromatin remodelers

118103Theoretical Physic