Chromatin fiber structure models

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

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. 

Fig. 12.2 DNA target models used for simulations. Gray DNA helix dark gray histone octamer black globular core of the linker histone H5. The chromatin fiber target model is represented in a simplified manner to improve the visualization of the structure. (According to Bernhardt et al. 2003, with permission)...

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... 

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].)...

The insight from AFM images may be greatly boosted by sophisticated image analysis. Fritzsche and Henderson [30,31] have extracted cross-sections of nucleosomes at half-maximum height and have fitted them to virtual ellipsoids. These ellipsoids had relatively smooth perimeter and an aspect ratio of 1.2 1.4 moreover, the orientation of the ellipsoids was correlated with the direction of the fiber axis, with more than 50% of nucleosomes aligned with the axis. While this orientation effect may result from surface interactions, as discussed by the authors themselves, it may also represent an actual, and structurally important, feature of fiber structure. Ellipsoid-shaped nucleosomes have been reported in electron EM studies [32,33], and have been predicted in models of chromatin... 

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. 

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... 

Figure 27-5 (A, B) Two possible models of the 30-nm chromatin fiber.55 (A) Thoma et al.85 (B) Woodcock et al.6i 87 The fully compacted structure is seen at the top of each figure. The bottom parts of the figures illustrate proposed intermediate steps in the ionic strength-induced compaction. (C) Possible organization of the DNA within a metaphase chromosome. Six nucleosomes form each turn of a solenoid in the 30-nm filament as in (A). The 30-nm filament forms 30 kb-loop domains of DNA and some of these attach at the base to the nuclear matrix that contains topoisomerase II. About ten of the loops form a helical radial array of 250-nm diameter around the core of the chromosome. Further winding of this helix into a tight coil 700 nm in diameter, as at the top in (C), forms a metaphase chromatid. From Manuelidis91.

A FIGURE 10-21 Solenoid model of the 30-nm condensed chromatin fiber in a side view. The octameric histone core (see Figure 10-20) is shown as an orange disk. Each nucieosome associates with one HI moiecuie, and the fiber coiis into a soienoid structure with a diameter of 30 nm. [Adapted from M. Grunstein, 1992, Sci. Am. 267 68.]... 

Figure 27-5 (A, B) Two possible models of the 30-nm chromatin fiber. (A) Thoma et alP (B) Woodcock et The fully compacted structure is seen at...

Figure 1. Hierarchical model of chromosome structure, (a) In interphase cells, DNA is packed in a nucleus as forming nucleosome and chromatin, (b) DNA forms nucleosome structure together with core histone octamer, which is then folded up into 30nm fiber with a help of linker histone HI. This 30 nm fiber is further folded into 80 nm fiber and 300 nm loop structures in a nucleus. In mitosis, chromosome is highly condensed. Proteins which are involved in each folding step are indicated above and non-protein factors are indicated below, (c) The amino acid sequences of histone tails (H2A, H2B, H3 and H4) are shown to indicate acetylation, methylation and phosphorylation sites. (See Colour Plate 1.)...

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. 

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. 

The association of poly(ADP-ribose) polymerase with chromatin has been well described by Aubin et al. (1) and by Butt et al. (2) and we have found die enzyme to be associated mainly with tri- and tetranucleosomes (1). Poly(ADP-ribosyl)ation in vitro has been found to alter chromatin structure by decondensation of the 30 mn fiber (3). Poly(ADP-ribose) polymerase win alter chromatin structure by the modification of core histones, linker histone HI and also by the interaction of automodified enzyme with chromatin. In this paper, we will review the different mechanisms by which poly(ADP-ribose) polymerase could modify specific nuclear proteins and alter chromatin stmcture. We present a model for the interaction of the enzyme with the various subnuclear components. 

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