Interrelationship between nuclear histone binding and cell proliferation

Abstract

1. 1. Binding of non-enzymatically [methyl- 14C]-labeled histone H3 to nuclei isolated from young and old rat livers, regenerating rat liver, and tumor cells has been investigated. 2. 2. Scatchard plot analysis indicated that various cell types had different binding capacity and different dissociation constant ( K d). 3. 3. Nuclei isolated from younger rats had fewer binding sites and lower K d (or higher K a) values for [methyl- 14C]H3 than those from older rats. 4. 4. Fewer binding sites and lower K d values were also observed with nuclei isolated from the maximally regenerating liver (24 hr after partial hepatectomy) and the fast-growing ascites tumor and Novikoff hepatomas. 5. 5. These results strongly suggest that the number of binding sites and affinity of histone H3 for nuclei appears to be correlated with the degree of cell proliferation. 6. 6. Fractionation of the [methyl- 14C]H3 bound nuclei into nuclear membrane and nucleoplasm demonstrates that approx. 94% of radioactivity is associated with the former in which less than 6% of DNA is found, whereas 94% of total DNA is found in nucleoplasm. 7. 7. This suggests that the binding of [methyl- 14C]H3 to nuclei is independent of DNA present in each fraction.