Metabolic behaviors of the core histones in proliferating Friend cells

Abstract

This study examines the turnover of the core histones in proliferating Friend cells. It was calculated that these proteins turn over with half-lives of 21.6 days for H2A, 13.8 days for H2B, 43.3 days for H3, and 138.6 days for H4. The significant differences in the half-lives of the four core histones indicate that the protein moiety of the nucleosome is not replaced as one entire unit but as a “mosaic” in which each component follows its own rate of replacement. In some experiments the turnover rates of the variants of H2A, H2B, and H3 were compared. The results did not indicate any differences among these histone variants, suggesting that they are not excluded from the mechanisms controlling histone turnover. Metabolic heterogeneity was discovered, however, when the turnover rates of the acetylated and nonacetylated molecules of histone H4 were followed: it appeared that the acetylated molecules are replaced 2.5 times faster. The comparison of the rate of replacement of the histones in proliferating and differentiated cells from one site and their level of acetylation from another suggests that this postsynthetic modification might be involved in the control of histone metabolism. Such a conclusion is supported also by a number of model experiments.