Histones as the Chromatin Skeleton

It has been shown in several biological assembly systems that, due to the fact that tertiary structure determines quaternary structure, a major component of the system can be assembled on its own to form structures similar to the intact organelle (Caspar and Klug, 1962). Ex- 

Histones were initially assumed to form part of an assembly system (Sperling and Bustin, 1974, 1975) for two reasons. First, they are present in chromatin as many copies of a few components. [The mass of the five histones equals that of the DNA (for references, see Phillips, 1971 Hnilica, 1972).] Second, fiber X-ray diffraction studies of chromatin (Luzzati and Nicolaieff, 1959 Wilkins et al., 1959 Pardon et al., 1967 Pardon and Wilkins, 1972) indicated that they are involved in a regular periodic structure. The fact that the histones are highly conserved with respect to their primary structure (Dayhoff, 1972 Wilson et al., 1977), especially the arginine-rich histones H3 and H4, also indicates that they may play a primarily structural role in which each residue is crucial. 

Since 1974, evidence has accumulated in the literature which indicates that chromatin itself may be considered as an assembly system. It is true that chromatin is more complex than assembly systems analyzed to date, both with respect to the size of the nucleic acid involved and therefore the amount (and variety) of protein complexed with it and with respect to the dynamic aspect of the multilevel higher order structure. Nevertheless, at least at the lower levels of organization, the interpretation of chromatin as an assembly system may be valid. Evidence for this derives from three basic lines of research described in previous sections (1) the reconstitution of the nucleosome, (2) the self-assembly of the octamer, and (3) the putative self-organization of nucleosomes into higher order structures. 

The fact that nucleosome-like particles can be reversibly reconstituted from histones and DNA, without any additional factor, exemplifies the principle of self-assembly of biological structures. The reconstituted particles have the characteristic beaded appearance of nu- 

The histone octamer is the histone unit of the nucleosome. As discussed in Section II, it has been shown that at high salt concentration (7 2 M) the core histones can assemble on their own, in the absence of DNA, to form histone octamers (this assembly occurs with both acid- and salt-extracted histones). Furthermore, the secondary and tertiary structures of core histones at high salt concentration are similar to the structures they have in the intact nucleosome. The basic units of the assembly of the four core histones are histone dimers which are obtained at low salt concentration. Upon increase in salt concentration, tetramers, hexamers, and octamers are obtained. The cross-linking pattern of histones in high salt concentration is similar to that in chromatin, again supporting the idea that the assembly of core histones at high salt concentration is similar to that in chromatin. 

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