Solenoids, chromatin structure

The basic structural imit of chromatin is the nucleosome, in which the DNA is wrapped 1.65 turns aroimd the histone octamer (H2A, H2B, H3, H4)2. The chromatin is further condensed to a so-called solenoid with the aid of histone HI. The following observations are relevant to the discussions about the role of chromatin structure in gene regulation (Lewin, 1994, Workman and Kingston, 1997, Kadonaga, 1998) ... 

The 100 A fiber can arrange itself into a solenoid or a 300 A fiber. The solenoid has a diameter of 300 A and a pitch of about 110 A. It is held together by HI histone interactions without the HI histone, the 100 A fibers are unable to form solenoids. Chromatin observed in the laboratory is largely an array of the 300 A fibers. The solenoids can be further compacted by twisting about themselves to form "knoblike" structures that are very compact and constitute the chromosomes. The organization of DNA into the 100 and 300 A (solenoid) fibers is shown in Figure 10.27. 

Repeating units of nucleosome plus linker DNA constitute the polynucleosome, which in turn is involved in higher orders of chromatin structure 50, 63,116,117,123,194). It has been postulated, based on electron micrographs, that polynucleosomes coil into a solenoid with 100 A hole through the central axis 50, 63, 116, 117, 123, 194) one turn of a helix includes 7 to 9 nucleosomes 171). 

Although the higher order structure of chromatin is still not well understood, two models have been suggested and supported by experimental evidence (for references, see Felsenfeld, 1978 Chambon, 1978). One is the solenoid model of Finch and Klug (1976), obtained by supercoiling the chromatin thread, and the other model is the superbead model (Renz et al., 1977). Each may represent a different... 

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].)...

McGhee, J.D., Nickol, J.D., Felsenfeld, G., and Rau, D.C. (1983) Higher order structure of chromatin orientation of nucleosomes within the 30 nm chromatin solenoid is independent of species and linker length. Cell 33, 831-841. 

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. 

Minsky et recently suggested that the emergence of eukaryotes led to a highly crowded environment that may have promoted DNA self-assembly, leading to extremely condensed and thermodynamically stable DNA aggregates such as nucleosomes and solenoid structures of chromatin. 

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.

Fig. 4. Schematic diagram of proposed solenoid structure of chromatin to yield a 30 nm fiber. The structure consists of six nucleosomes per turn of the helix and hence would be three nucleosomes wide. In the diagram, only three nucleosomes of each turn are visible the other three nucleosomes per turn are hidden from view.

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.]... 

Studies of the condensed chromatin fibre structure and the condensation mechanism have resulted in basically two classes of models models based on a helical arrangement of nucleosomes along the fibre and those based on a linear array of globular nucleosome clusters (superbeads) along the fibre. The first class includes the solenoid, twisted ribbon and crossed linker models whereas the latter are the superbead models and related layered structures. Schematic representations of some models are shown in Fig. 10. 

Figure 7.7 Chromatin Filament to Chromosome, (a) Proposed model of the 300 A chromatin filament. The zigzag pattern of nucleosomes (1,2,3,4) closes up to form a solenoid with 6 nucleosomes per turn, (b) Model of histone HI binding to the DNA of the nucleosome. (c) X-ray crystal structure of the nucleosome core particle. Two views are illustrated (top-left and side-right) showing histone octamer in ribbon structure form (H2A yellow H2B red H3 blue H4 green) (illustrations a), b) and c). Reproduced from Voet, Voet Pratt, 1999 [Wiley], Figs. 23-48, 23-45 and 23-44 respectively).

Fig. 21-5 Different levels of DNA structure, (a) Double helix, (b) Chromatin fiber, (c) Solenoidal fiber.

It has been proposed that nucleosomes are arranged in chromatin in higher ordered structures termed solenoids [5]. The solenoid has been shown to have about six to eight nucleosomes per turn [6]. Since highly complex polymers have about six to... 

This causes a relaxation of these structures (Fig. 5c,d) and this correlates well with the formation of the hyper(ADP-ribosyl)ated forms of histone HI (Fig. 4). It is tempting to suggest that the destabilization of these toroidal structures, resulting from the interaction between histone HI and DNA, is similar to what has been observed in the relaxation of the solenoid conformation by poly(ADP-ribose) polymerase [6, 7]. Our results strongly suggest that poly(ADP-ribosyl)ation of the chromatin and its subsequent structural relaxation are probably tightly coupled to the interaction between histone HI and DNA. 

Postsynthetic modifications of histones, i.e., phosphorylation, acetylation, and poly(ADP-ribosylation), have been suggested to be involved in the modulation of the structure and the function of chromatin [7, 8]. A central role has been attributed to histone HI in forming and stabilizing the nucleosomal structure and the higher order folding of the polynucleosomal chain into a solenoid conformation [8-10]. 

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