DNA and histones

Histone acetylation is a reversible and covalent modification of histone proteins introduced at the e-amino groups of lysine residues. Histones and DNA form a complex - chromatin - which condenses DNA and controls gene activity. Current models interpret histone acetylation as a means to regulate chromatin activity. 

Some of this differential expression is achieved by having different regions of chromatin available for transcription in cells from various tissues. For example, the DNA containing the P-globin gene cluster is in active chromatin in the reticulocyte but in inactive chromatin in muscle cells. All the factors involved in the determination of active chromatin have not been elucidated. The presence of nucleosomes and of complexes of histones and DNA (see Chapter 36) certainly provides a barrier against the ready association of transcription fac-... 

During nucleosome reconstitution, performed by mixing core histones and DNA in 2 M NaCl with slow back-dialysis to low salt con-... 

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-... 

Despite the apparent symmetry of the histones within the core particle, deviations of the histones and DNA result in an asymmetric structure. In the histones, these deviations can occur throughout protein structure, not just in the relatively unstructured tails (Fig. 6). The most pronounced deviations appear in histone H3. 

In this chapter we have presented a brief struetural overview of the modifications of the primary structure and at the post-translational level that contribute to histone variability. We have also diseussed the different contributions of histones and DNA to the stability and dynamies of the ehromatin nucleoprotein complex. In Section 6 we have integrated both topies using several representative examples from experimental results available from reeent and past literature. The results described in this section provide a good example of the dual informational and structural role of histone variability. 

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... 

The self-assembly of this fundamental building block of chromatin is a topic of enduring interest. DNase I digestion experiments as well as spectroscopic studies indicate that nucleosome core particles can be reconstituted by salt-jump (i.e., diluting NaCl concentration from 2.0 to 0.2 M) or by direct mixing of histones and DNA at the lower salt concentration. Daban and Cantor used the increase in eximer fluorescence to investigate the reassembly process in terms of a two-state model ... 

Komberg, R.D. (1974) Chromatin structure a repeating unit of histones and DNA. Science 184, 868-871. 

Figure 3. Proposed fimction of polymalate (PMA) in the rqiroduction of certain molds and fungi according to E. Holler (see references cited in [2]). Like DNA, PMA is an anionic polyelectrolyte, while the histones and DNA polymerase are proteins with high content of amino-acid residues carrying positively changed, cationic side chains (histidine, lysine, arginine).

The acetylation of the lysine side chain neutralizes the positive charge of the lysine and hence will loosen the association between the histone and DNA. This should facilitate greater access of enzymes to the DNA sequence. 

The high ionic strength (high salt concentration) shields the charges on the histones and DNA and enables the proteins to dissociate from the DNA. Electrostatic interactions are rendered much weaker in a high-ionic-strength environment. 

---