The nature and physicochemical properties of histones

Abstract

The electrophoretic analysis of histones extracted from the cell nuclei isolated from a number of different tissues and species has shown that, while there are some exceptions, these consist in general of three components which have been termed α-, β-, and y-histones. The α- and y-components are not, however, necessarily homogeneous proteins, for in those cases where it has been possible to fractionate the total histone either by chemical methods or by sedimentation or by a combination of both these procedures, the former has been found to consist of at least three components and the latter probably of two. The components of the a-fraction have been distinguished by the symbols a1a2, and a3, respectively. The β-histones correspond essentially to the ‘main’, and the a- and y-fractions to the ‘subsidiary’, histones of the earlier provisional nomenclature. The β-histones possess the typical composition of traditional histones. They are further characterized by their ability to form aggregates of increasing size as the pH’s of their solutions are raised, a phenomenon brought to light by measurements of their diffusion coefficients and sedimentation constants. Subsidiary histones differ from β-histones both in amino acid composition and in physical properties. In particular, they do not exhibit the phenomenon of aggregation shown by the latter. Nevertheless, all of them resemble the β-histones in possessing strongly basic properties, a fact which is evident from their mobility-pH curves. The isoelectric points of a number of β-histones have been determined from such curves. Further evidence supporting the conception that histones are cell-specific is recorded. This has been provided mainly by a study of abnormal cells. Only small differences in isoelectric points and in electrophoretic mobilities have so far been detected between the β-histones from the liver cells and thymocytes of the ox. Examination of the histones from a number of tumours, both natural and experimental, has shown that β-histones from these sources usually differ from normal β-histones in possessing much smaller solubilities and electrophoretic mobilities and markedly greater capacities to aggregate. No combination occurs between histone and azo dye during the induction of hepatomas in rats by this carcinogen. Some dye is nevertheless bound in the nucleus during the induction period. It is presumably bound by chromosomin. It is concluded that the carcinogenic action of the dye is due to its combination with, and consequent modification or inhibition of, one or more genes. In conformity with the results of this and former investigations the terms protamin and histone have been defined more precisely than has hitherto been possible.