In chromatin

All steps—from changes in DNA template, sequence, and accessibility in chromatin to RNA stability—are subject to modulation and hence are potential control sites for eukaryotic gene regulation. 

Finally, the binding of specific transcription factors to cognate DNA elements may result in disruption of nucleosomal structure. Many eukaryotic genes have multiple protein-binding DNA elements. The serial binding of transcription factors to these elements—in a combinatorial fashion—may either directly disrupt the structure of the nucleosome or prevent its re-formation or recruit, via protein-protein interactions, multiprotein coactivator complexes that have the ability to covalently modify or remodel nucleosomes. These reactions result in chromatin-level structural changes that in the end increase DNA accessibifity to other factors and the transcription machinery. 

Grunstein M Histone acetylation in chromatin structure and transcription. Nature 1997 389 349. 

WUson CJ, Chao DM, Imbalzano AN, Schnitzler GR, Kingston RE, Young RA (1996) RNA polymerase II holoenzyme contains SWI/SNF regulators involved in chromatin remodeling. Cell 84(2) 235-244... 

Nackerdien, Z., Olinski, R. and Dizdaroglu, M. (1992). DNA base damage in chromatin of 7-irradiated human cells. Free Rad. Res. Commun. 16, 259-273. 

An additional question relating to sites of modification is the possible influence of DNA binding proteins and the conformational changes they induce in DNA as it forms chromatin, which in turn may influence available binding sites for adduct formation. Several studies have investigated the distribution of DNA adducts in chromatin (95-102). although no clear answer for the influence of these proteins has yet emerged. 

In isolated nuclei from rat liver and kidney, Ni2 + was bound to chromatin, polynucleosomes and to deproteinized DNA [339]. Ni2+ directly interacted with stable binding sites on the DNA molecule in chromatin and was associated with histone and nonhistone nuclear proteins [339, 340]. 

The aim of this article is to present evidence and to develop a hypothesis concerning the dynamic structural role of histones in chromatin. 

During the course of the article, we will present evidence that the histones constitute part of a self-assembly system (Section IV). In the absence of DNA they retain the information to interact with each other to form a hierarchy of structures with dimensions, periodicities, and intermolecular contacts, compatible with what is known about the protein core of chromatin. This strongly suggests that histone-histone interactions have a fundamental role in chromatin structure. 

I. Comparison of Histone-Histone Contacts in Chromatin with... 

Histones at High Salt—Similar to Histones in Chromatin... 

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. 

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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