Patterns of Histone Acetylation in the Cell

Labeling of histones in the naturally synchronous cell cycle of Physarum polycephalum with short pulses of tritiated acetate in vivo clearly showed three distinct patterns of histone acetate turnover. In G2 phase, turnover of acetate was observed only in histones H3 and H4, predominantly on the multiple acetylated forms. No acetate turnover was found in histones H2A and H2B. This indicates different functional roles of histones H2A and H2B compared with histones H3 and H4. In S phase, intense labeling was seen in all four core histones, in histones H3 and H4 predominantly in the low Chromatin is involved in several of the key processes of living cells, particularly transcription, replication, and distribution of the genetic material to daughter cells. These processes are associated with different structural states of the chromatin, and although very substantial progress has been made in un- derstanding the structure of the underlying nucleosome sub- unit, there remains much speculation about how the nucleo- some structure is modified to accommodate different chro- matin functions and about higher order packing of nucleosomes in the different chromatin structures (for a review, see Igo- Kemenes et al. (1982)l. There are two key questions being asked about the chromosome structural transitions. First, what signals determine when a particular transition should occur and where it occurs, relative to specific DNA sequences in the chromatin. Second, what are the characteristics of each specific state of the chromatin that stabilize that state and enable it to function in its specific role? We are concerned, here, with the second question and with the role of histone modification in stabilizing specific chromatin structures. Acetylation of core histones has previously been correlated with chromosome replication and transcription and negatively correlated with mitosis (for a review, see Matthews & Brad- bury (1 982)). However, many of the systems used to establish these correlations did not have total separation of replicating from transcribing chromatin, and results from chromatin fractionation procedures have shown variable amounts of acetylated histones associated with "active" chromatin. We have reinvestigated the relationship between histone acetylation and chromatin function by using an in vivo, unperturbed system in which three situations are available with a purity