Regulation of global acetylation in mitosis through loss of histone acetyltransferases and deacetylases from chromatin

Histone acetylation, a reversible modification of the core histones, is wid ely accepted to be involved in remodeling chromatin organization for geneti c reprogramming. Histone acetylation is a dynamic process that is regulated by two classes of enzymes, the histone acetyltransferases (HATs) and histo ne deacetylases (HDACs). Although promoter-specific acetylation and deacety lation has received most of the recent attention, it is superimposed upon a broader acting and dynamic acetylation that profoundly affects many nuclea r processes. In this study, we monitored this broader histone acetylation a s cells enter and exit mitosis. In contrast to the hypothesis that RATs and HDACs remain bound to mitotic chromosomes to provide an epigenetic imprint for postmitotic reactivation of the genome, we observed that RATs and HDAC s are spatially reorganized and displaced from condensing chromosomes as ce lls progress through mitosis. During mitosis, HATs and HDACs are unable to acetylate or deacetylate chromatin in situ despite remaining fully catalyti cally active when isolated from mitotic cells and assayed in vitro. Our res ults demonstrate that HATs and HDACs do not stably bind to the genome to fu nction as an epigenetic mechanism of selective postmitotic gene activation. Our results, however, do support a role for spatial organization of these enzymes within the cell nucleus and their relationship to euchromatin and h eterochromatin postmitotically in the reactivation of the genome.