Nucleic acids and chromatin
Nucleic acids and chromatin

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Nucleic acids and chromatin

The histone proteins

The genes for the histone proteins are very highly conserved across eukaryotes, reflecting their importance in DNA packaging. The histone family consists of five groups of proteins, histones H1, H2A, H2B, H3 and H4. An examination of their amino acid content gives us clues as to how the histones fulfil their role in DNA packaging. Rather like the polyamines in bacteria, these proteins are highly positively charged, with up to 20% of their amino acids being lysine or arginine, the charged side-chains serving to counteract the negative charges of the phosphate groups on the double helix backbone.

Further analyses of the genes for the histones H2A, H2B, H3 and H4 reveal that they have highly similar sequences, suggesting that this gene family arose from a single common ancestral gene, most likely through gene duplication. An example of how highly conserved these genes are is seen in the amino acid sequence of histone H4, which differs by only two amino acids over 102 residues between such evolutionarily distant species as the pea and the cow. Histones H2A, H2B, H3 and H4 are collectively known as the ‘core’ histones and all share a common structural motif called the histone fold, comprising three helices connected by two loops (Figure 27). This histone fold provides the basic unit of DNA packaging in eukaryotic cells.

Outside of the region of the histone fold, the N-terminus of the histone forms a ‘tail’ comprising between 20 and 40 amino acids and having no defined secondary structure. The histone tails are very rich in lysine residues. These positively charged residues serve as targets for various secondary modifications such as methylation or acetylation which can neutralise their charge. Such modifications play a key role in the regulation of chromatin structure and will be discussed in more detail shortly.

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