Histones are the main proteins that interact with DNA to assemble nucleosomes, which in turn form chromatin chains, expressed as chromosomes in eukaryotic organisms. In other words, the long chain of a DNA molecule, twisted like a wire onto the octameric core, allows for packing the entire molecule into the nucleus. Due to this, 46 DNA molecules of the diploid human genome with a total length of about two meters, containing a total of six billion base pairs, can fit into the cell nucleus with a diameter of only 10 µm (fig. 1).
Histones are in direct contact with DNA on the principle of electrostatic bonds, as they can neutralise the negative charge of DNA phosphate groups due to positive charges of amino acid residues. In particular, two molecules of each of the histones, H2A, H2B, H3, and H4, form an octamer around which 146 DNA base pairs are wrapped. At the same time, the ninth protein, H1, does not enter the histone core but binds to the linker DNA.
All histones have only five types of proteins: H1, H2A, H2B, H3, and H4. Each of them has an increased alkaline nature justified by its high content of lysine and arginine. Besides five original proteins, there is a whole range of their modifications, which are expressed during the whole life cycle. Most of them, as well as canonical histones, are evolutionarily conservative, which indicates an indispensable role in the vital activity of cells.
The regulatory action of histone chromosomal proteins was investigated through molecular biology methods. Thus, in addition to the structure-forming function, histones play an essential role in regulating gene expression at the transcription stage and chromatin rearrangement. Throughout the whole existence, histone molecules undergo modifications: it can be acetylation and methylation of lysine residues, which will lead to the loss of positive charge, or phosphorylation of serine residues, which will lead to the appearance of negative charge.
The “silencing” state, typical for most eukaryotic genes, can be achieved by a unique compact stacking of chromatin, which is formed by DNA interaction with histones. For example, phosphorylation of serine residues in positions 10 and 28 of histone H3 is a marker of low transcription activity. In contrast, the combination of histone acetylation and histone phosphorylation effectively reduces the positive charge of histones, and this can disrupt electrostatic interactions between histones and DNA. In turn, this results in a less compact chromatin structure, thus facilitating access to DNA by protein mechanisms such as those involved in transcription. In general, it is assumed that multiple modifications occurring at specific histone sites are code that affects which proteins are capable of interacting with histone and DNA complexes and therefore which these genes regulate proteins.