Conformations and flexibilities of histones and high mobility group (HMG) proteins in chromatin structure and function.

The packaging of the enormous lengths of eukaryotic DNA into the different conformational states of chromosomes is controlled very largely by an equal total mass of the histones, H1, H2A, H2B, H3 and H4. Histone sequences, sequence conservations, postsynthetic chemical modifications and studies of histone conformations and interactions show clearly that histones are multi-domain proteins. The N-terminal domains of all histones and the C-terminal domains of H1, H2A and H2B are flexible random coils, while the C-terminal regions of H3 and H4 and the central regions of H1, H2A and H2B are structured. Histones H3 and H4 are essential for nucleosome structure and interact with DNA to give the nucleus of the nucleosome structure, which is completed by interactions of the conserved structured regions of (H2A, H2B) dimers and H1. The flexible domains of all the histones are very basic and contain all the sites of reversible chemical modifications: acetylation of lysines in the core histones and phosphorylation of serines and threonines in histone H1. Strict correlations have been observed (i) between acetylation and DNA processing and (ii) between H1 phosphorylation and chromosome condensation. In addition to histone acetylation, active chromatin is also associated with high mobility group (HMG) proteins 14 and 17. These proteins are completely flexible under all solution conditions and their native structures must be imposed by their binding sites in active chromatin. The function of flexibility in these chromosomal proteins is not understood but is probably related to the enormous lengths of DNA which have to be controlled in the structures and function of chromosomes.