Changes in core histone variant composition in differentiating neurons: the roles of differential turnover and synthesis rates.

The core histone classes H2A, H2B, H3, and H4 are the main group of proteins responsible for the folding of DNA in nucleosomes. Each of the core histone classes except H4 is composed of nonallelic variants. The core histone variant composition changes during postnatal development in rat cerebral cortex neurons; H2A.1, H2B.1, H3.1 and H3.2 decay exponentially, whereas H2A.2, H2A.x, H2B.2, and H3.3 accumulate. H2A.z is the only variant that remains constant. We have studied the synthesis of core histone variants in cortical neurons and their neuroblasts by in vivo labeling with [14C]lysine. The variant synthesis pattern of neuroblasts has been determined by labeling gravid rats during the period of proliferation of the brain cortical neurons of the fetuses, and synthesis in neurons has been studied by postnatal labeling. The incorporation of H2A.1 is about twice that of H2A.2, both in neurons and neuroblasts. Despite its higher synthesis rate, the proportion of H2A.1 decreases during postnatal development indicating that the turnover of H2A.1 is faster than that of H2A.2. Differential turnover and a change in synthesis rate are both involved in determining the relative concentrations of H2B.1 and H2B.2 in neurons. H3.1 and H3.2 are synthesized in neuroblasts, but not in neurons, and are thus replaced by H3.3 in neuronal chromatin. The fact that the synthesis pattern of immature neurons from newborns does not differ from that of mature neurons indicates that the changes in the synthesis pattern of core histones occur at the arrest of cell proliferation and are unrelated to the state of differentiation of the cells.