Histones

Autoantibodies to histone antigens have been described in patients with idiopathic and drug-induced SLE, rheumatoid arthritis, and other conditions. Histones are a group of similar, small, highly conserved nuclear proteins that bind to DNA by their many basic residues. The presence of autoantibodies to histones are frequently found in several rheumatic disorders (1). In one study, the predominant responses to histones in SLE sera were to H1, H2b, and H3. Marked elevations of binding occurred to H1 and H2b in 33% of patients, while 25% showed higher binding to H3 (2). The same study showed the highest anti-histone reactivity to be in patients with rheumatoid arthritis with vasculitis, while the highest reactivity in SLE sera was in those patients with a history of photosensitivity (3). In diploid eukaryotic cells, the chromatin fibers are about 20nM in diameter. They consist of two major components in equal amounts, DNA and basic proteins called histones. The histones are a group of water and dilute acid soluble basic proteins found associated with DNA in chromosomes. They are characterized by relatively high levels of lysine and arginine. Although histones are classified into a limited number of types of fractions (see below) with each particular fraction having a fundamentally distinct amino acid composition and sequence, numerous subfractions are observed due to the acetylation, methylation, and phosphorylation of various amino acid residues. Microheterogeneity or alteration of structure is dynamic such that the histones of a single cell type are found to vary during development. They are believed to play a role in gene activity and cellular metabolism. Histones are believed to be regularly arranged in the deep groove of the DNA helix. The recurring positive charges of the histones form electrostatic associations with the negatively charged phosphate groups of DNA making the DNA more stable and flexible. This allows for the supercoiling of the chromatin fibers. With the exception of H1, the primary structures of the calf thymus histones have been determined. Comparisons with the structures for histones from other sources indicate that the histones rank among the most highly conserved (low mutation rate) proteins in nature. The nucleoprotein complex of histone and deoxyribonucleic acid is referred to as nucleohistone or deoxyribonucleoprotein. It is important as a source of its two components as well as an entity in itself for physical studies. Intracellularly, these complexes may be important factors in chromosomal structure and gene transcription. Kornberg (1974) has proposed a model for chromatin in which 200 DNA base pairs are coiled on the outside of a histone unit composed of (H3)2(H4)2 tetramer and two each of H2a and H2b. Molecular Weights of Histones: Lysine Rich (H1, f1): ~ 21,500 Slightly Lysine Rich (H2a, f2a2): 14,004 Slightly Lysine Rich (H2b, f2b): 13,774 Arginine Rich (H3, f3): 15,324 Arginine Rich (H4, f2a1): 11,282