Stimulatory effect of histones on phosphorylation of nuclear phosphoproteins.

Effect of histones on phosphorylation of nuclear phosphoproteins was studied using two species of phosphoprotein kinases with different kinetic and catalytic properties; namely, protein kinases A1 and A2 (Takeda, M., Matsumura, S., & Nakaya, Y. (1974) J. Biochem. 75, 743-751). The reaction rate for protein kinase A1 was markedly enhanced when histone or polylysine was added to the reaction mixture. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the basic protein served as a stimulator rather than acted as a substrate in this reaction. In contrast, when protein kinase A2 was employed, the stimulatory action of these basic proteins was less marked than for protein kinase A1. It seems likely that the phosphorylation of nuclear phosphoproteins, particularly the reaction catalyzed by protein kinase A1, may be strongly influenced by histones which are integrated in the chromatin structure.     

Pharmacological effect of exogenous histones on muscles

Different histone fractions contain sequences homologous to those of several regulatory peptides. All the histone fractions demonstrated dose-dependent positive chronotropic effect in spontaneously contracting rat atrial preparations. The range of their activity was as follows: H4 greater than H1 greater than H2a much greater than H3. Synthetic COOH-terminal histone H4 pentapeptide (historphin) Tyr-Gly-Phe-Gly-Gly demonstrated opioid activity by inhibiting electrostimulated guinea-pig ileal contractions. It is suggested that some biological activities of histones are related to the presence of regulatory peptide sequences in their structure.     

The self-association of chicken-erythrocyte histones.

The self-association of the separate histone fractions isolated from chicken erythrocytes has been studied in solution at a number of different pH values and ionic strengths. The apparent molecular weights of the histones were determined over a range of macromolecular concentrations using the techniques of osmotic pressure and sedimentation equilibrium. Histone F2c (H5) did not associate under any of the conditions investigated whereas the other histone fractions all appeared to undergo self-association forming dimers, dimers of dimers, etc. The degree of association increased with the pH and ionic strength of the medium. The tendency to aggregate increased in the order; histone F2c (H5) (non-aggregating), histone F2b (H2B), histone F2a2 (H2A), histone F3 (H3), histone F2a1 (H4) (highly aggregating). In the case of histone F2a2 (H2A) at pH 3.0 and ionic strength 0.1, the apparent weight-average molecular weight was determined at a number of macromolecular concentrations at five different temperatures. The self-association was analysed according to the method of Adams (published by Beckman Instruments Inc. in 1967) and shown to be a monomer-dimer-tetramer equilibrium. The association constants were evaluated at each of the temperatures studied and from their variation with temperature the values of the enthalpy and entropy of association were calculated. The intermolecular association was characterised by only a small change in enthalpy but a large, positive, change in entropy. This suggests that the association of histones at acid pH is due to hydrophobic interactions between the relatively uncharged segments of like polypeptide chains.     

Sequential ADP-ribosylation pattern of nucleosomal histones. ADP-ribosylation of nucleosomal histones

The pattern of nucleosomal histones poly(ADP-ribosyl)ation is changed under conditions which affect the poly(ADP-ribosyl)ation state of the enzyme. At low NAD concentrations the enzyme can poly(ADP-ribosyl)ate histones H1 and H1, H2A, A2A, and H2B. However at NAD concentrations above 10 microM the enzyme preferentially poly(ADP-ribosyl)ates histone H1 to a hyper ADP-ribosylated form. Furthermore we have observed hyper ADP-ribosylation of histone H2B at NAD concentrations of 10 microM suggesting that histone H2B can undergo the same type of ADP-ribosylation pattern as histone H1. Also at higher NAD concentrations an elongation of the polymer attached to the enzyme and other nuclear proteins takes place.     

The evolution of histones

Summary The amino acid sequences of bovine histones H2A, H2B, H3, and H4 and the first 107 residues of rabbit thymus histone H1 were examined using newly developed procedures designed to detect and evaluate weak similarities (de Haën et al., 1976). Using the McLachlan scoring system, regions of statistically significant similarity were found between several pairs of the four smallest histones. The probability that this set of similarities could result simply from chance was estimated to be less than 10^–5. No similarity was found between the H1 sequence and the other histones. The results are interpreted to indicate that at least the C-terminal portions of the core histones evolved from a common ancestral protein.