The two-angle model and the phase diagram for Chromatin

We have studied the phase diagram for chromatin within the framework of the two-angle model. Rather than improving existing models with finer details our main focus of the work is getting mathematically rigorous results on the structure, especially on the excluded volume effects and the effects on the energy due to the long-range forces and their screening. Thus we present a phase diagram for the allowed conformations and the Coulomb energies

The influence of the cylindrical shape of the nucleosomes and H1 defects on properties of chromatin

We present a model improving the two-angle model for interphase chromatin (E2A model). This model takes into account the cylindrical shape of the histone octamers, the H1 histones in front of the nucleosomes and the vertical distance $d$ between the in and outgoing DNA strands. Factoring these chromatin features in, one gets essential changes in the chromatin phase diagram: Not only the shape of the excluded-volume borderline changes but also the vertical distance $d$ has a dramatic influence on the forbidden area. Furthermore, we examined the influence of H1 defects on the properties of the chromatin fiber. Thus we present two possible strategies for chromatin compaction: The use of very dense states in the phase diagram in the gaps in the excluded volume borderline or missing H1 histones which can lead to very compact fibers. The chromatin fiber might use both of these mechanisms to compact itself at least locally. Line densities computed within the model coincident with the experimental values

Monte Carlo Simulations indicate that Chromati: Nanostructure is accessible by Light Microscopy

A long controversy exists about the structure of chromatin. Theoretically, this structure could be resolved by scattering experiments if one determines the scattering function - or equivalently the pair distribution function - of the nucleosomes. Unfortunately, scattering experiments with live cells are very difficult and limited to only a couple of nucleosomes

Isotropic actomyosin dynamics promote organization of the apical cell cortex in epithelial cells

Although cortical actin plays an important role in cellular mechanics and morphogenesis, there is surprisingly little information on cortex organization at the apical surface of cells. In this paper, we characterize organization and dynamics of microvilli (MV) and a previously unappreciated actomyosin network at the apical surface of Madin–Darby canine kidney cells. In contrast to short and static MV in confluent cells, the apical surfaces of nonconfluent epithelial cells (ECs) form highly dynamic protrusions, which are often oriented along the plane of the membrane. These dynamic MV exhibit complex and spatially correlated reorganization, which is dependent on myosin II activity. Surprisingly, myosin II is organized into an extensive network of filaments spanning the entire apical membrane in nonconfluent ECs. Dynamic MV, myosin filaments, and their associated actin filaments form an interconnected, prestressed network. Interestingly, this network regulates lateral mobility of apical membrane probes such as integrins or epidermal growth factor receptors, suggesting that coordinated actomyosin dynamics contributes to apical cell membrane organization

Depletion Effects Massively Change Chromatin Properties and Influence Genome Folding

We present a Monte Carlo model for genome folding at the 30-nm scale with focus on linker-histone and nucleosome depletion effects. We find that parameter distributions from experimental data do not lead to one specific chromatin fiber structure, but instead to a distribution of structures in the chromatin phase diagram. Depletion of linker histones and nucleosomes affects, massively, the flexibility and the extension of chromatin fibers. Increasing the amount of nucleosome skips (i.e., nucleosome depletion) can lead either to a collapse or to a swelling of chromatin fibers. These opposing effects are discussed and we show that depletion effects may even contribute to chromatin compaction. Furthermore, we find that predictions from experimental data for the average nucleosome skip rate lie exactly in the regime of maximum chromatin compaction. Finally, we determine the pair distribution function of chromatin. This function reflects the structure of the fiber, and its Fourier-transform can be measured experimentally. Our calculations show that even in the case of fibers with depletion effects, the main dominant peaks (characterizing the structure and the length scales) can still be identified

Histone Depletion Facilitates Chromatin Loops on the Kilobasepair Scale

The packing of eukaryotic DNA in the nucleus is decisive for its function; for instance, contact between remote genome sites constitutes a basic feature of gene regulation. Interactions among regulatory proteins, DNA binding, and transcription activation are facilitated by looping of the intervening chromatin. Such long-range interactions depend on the bending flexibility of chromatin, i.e., the ring-closure probability is a directly measurable indicator of polymer flexibility. The applicability of a wormlike chain model to naked DNA has been widely accepted. However, whether this model also suffices to describe the flexibility of eukaryotic interphase chromatin is still a matter of discussion. Here we compare both 5C data from a gene desert and data from fluorescence in situ hybridization with the results of a Monte Carlo simulation of chromatin fibers with and without histone depletion. We then estimate the ring-closure probabilities of simulated fibers with estimates from analytical calculations and show that the wormlike chain model grossly underestimates chromatin flexibility for sharp bends. Most importantly, we find that only fibers with random depletion of linker histones or nucleosomes can explain the probability of random chromatin contacts on small length scales that play an important role in gene regulation. It is possible that missing linker histones and nucleosomes are not just simple, unavoidable, randomly occurring defects, but instead play a regulatory role in gene expression