Chromatin fiber models

Thus, to reflect correctly the state of the system at a certain temperature, one needs a simulation technique that generates an ensemble of chain conformations whose statistical properties reflect those of the real chain at thermodynamic equilibrium. The chromatin fiber models that are discussed in the following use one or the other variation of such techniques. 

Simpson RT, Thoma F, Brubaker JM (1985) Chromatin reconstituted from tandemly repeated cloned DNA fragments and core histones a model system for study of higher order structure. Cell 42 799-808 Sugiyama S, Yoshino T, Kanahara H, Kobori T, Ohtani T (2003) Atomic force microscopic imaging of 30 nm chromatin fiber from partially relaxed plant chromosomes. Scanning 25 132-136 Sugiyama S, Yoshino T, Kanahara H, Shichiri M, Fukushi D, Ohtani T (2004) Effects of acetic acid treatment on plant chromosome structures analyzed by atomic force microscopy. Anal Biochem 324 39 4... 

A. Lesne, and J. M. Victor, Chromatin fiber functional organization Some plausible models. 

C. L. Woodcock, S. A. Grigoryev, R. A. Horowitz, and N. Whitaker, A chromatin folding model that incorporates linker variabihly generates fibers resembling the native structures. Prvc. Natl. 

With the demise of the uniform fiber model in 1974, it became necessary to devise other models to account for the early electron micrographs of chromatin fibers and the X-ray diffraction studies (see Ref. [1], Chapter 1). Two models appeared in 1976, and were the major contenders for consideration in 1978. The superbead model of Franke et al. [36] envisioned the chromatin fiber as a compaction of multi-nucleosome superbeads . The solenoid model of Finch and Klug [37] postulated a regular helical array of nucleosomes, with approximately six nucleosomes per turn and a pitch of 10 nm. Although a number of competing helical models appeared in the 1980s (see Ref. [1], Chapter 7) the solenoid model remains a serious contender to this day. Structural details of this model, such as the precise disposition of linker DNA, are still lacking. 

Fig. 7. Cross-linker model for nucleosome arrangement in the chromatin fiber superstructure in the presence (a) or absence (b) of H1/H5, based on data in the literature (see text) and H5-containing mono-nucleosome stem structure in Fig. 3(c). In 3D, the plane of the nucleosomes is expected to rotate more or less regularly around the fiber axis, forming a solenoid-like superstructure. Nucleosomes 1, 2 and 5 are in the open conformation of Fig. 3(a), nucleosomes 4 and 7 in the open conformation of Fig. 2(b), and other nucleosomes in the closed negative (Fig. 2(c)) or positive conformations. Nucleosomes are expected to thermally fiuctuate between the different conformations, within an overall dynamic equilibrium of (ALkn) -l (see text). -I- and - refer to node polarities. (From Fig. 5 in Ref. [28].)...

Beard, D.A. and Schlick, T. (2001) Computational modeling predicts the structure and dynamics of chromatin fiber. Structure (Camb) 9, 105-114. 

Woodcock, C.L., Grigoryev, S.A., Horowitz, R.A., and Whitaker, N. (1993) A chromatin folding model that incorporates linker variability generates fiber resembling the native structures. Proc. Natl. Acad. Sci. 1 90(19), 9021-9025. 

Theoretical models of chromatin fibers and their simulated AFM images support the view that extended chromatin fibers are irregular three-dimensional arrays of nucleosomes connected by straight linkers... 

The structure of the condensed chromatin fiber is still under discussion [1,23,54], with two competing models the original solenoid model of Finch and Klug [16], and the straight-linker model [12,14,55]. Assessing the structure in vivo or in situ has proven impossible thus far, due to technical limitations. Chromatin fibers released from nuclei into solution by nuclease treatment have been widely used as models for fiber structure such fibers are extended at low ionic strength and condensed at ionic strengths believed to be close to those found in vivo ( 150 mM Na" " or 0.35 mM Mg " "). The salt-induced fiber compaction has been extensively studied in the past but is still poorly understood in terms not only of the details of the structure but also in terms of the molecular mechanisms of the compaction process. 

Images obtained by cryo electron microscopy should in principle be able to distinguish between the structural features proposed by the different models mentioned above [16]. The micrographs show a zig-zag motif at lower salt concentrations and they indicate that the chromatin fiber becomes more and more compact when the ionic strength is raised towards the physiological value (i.e., about 150 mM monovalent ions). 

From the physics point of view, the system that we deal with here—a semiflexible polyelectrolyte that is packaged by protein complexes regularly spaced along its contour—is of a complexity that still allows the application of analytical and numerical models. For quantitative prediction of chromatin properties from such models, certain physical parameters must be known such as the dimensions of the nucleosomes and DNA, their surface charge, interactions, and mechanical flexibility. Current structural research on chromatin, oligonucleosomes, and DNA has brought us into a position where many such elementary physical parameters are known. Thus, our understanding of the components of the chromatin fiber is now at a level where predictions of physical properties of the fiber are possible and can be experimentally tested. 

In an early attempt to model the dynamics of the chromatin fiber, Ehrlich and Langowski [96] assumed a chain geometry similar to the one used later by Katritch et al. [89] nucleosomes were approximated as spherical beads and the linker DNA as a segmented flexible polymer with Debye-Huckel electrostatics. The interaction between nucleosomes was a steep repulsive Lennard-Jones type potential attractive interactions were not included. 

The state of our understanding of the physics of chromatin folding is such that the current knowledge about the structure and interaction of the basic components of chromatin— histones and DNA—enables us to develop the first quantitative models of the structure and dynamics of the chromatin fiber. Even so, these models are still at a very rudimentary stage data on the interaction of the histone tails... 

Gebe, J.A., Allison, S.A., Clendenning, J.B., and Schurr, J.M. (1995) Monte-Carlo simulations of supercoiling free-energies for unknotted and trefoil knotted DNAs. Biophys. J. 68, 619-633. Beard, D.A. and Schlick, T. (2001) Computational modeling predicts the structure and dynamics of chromatin fiber. Structure 9, 105-114. 

Ehrlich, L., Munkel, C., Chirico, G., and Langowski, J. (1997) A Brownian dynamics model for the chromatin fiber. Comput. Appl. Biosci. 13, 271-279. 

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