Accessibility of newly synthesized chromatin to histone acetylase.

Pulse-chase experiments with [3H]lysine-labeled tissue culture cells reveal that newly synthesized nucleosomal histones H2B, H3, H4 (and possibly H2A) in chromatin are more accessible to histone acetylase in vivo than are older, pre-existing histones. Thus, when rat hepatoma cells are first pulse-labeled and then incubated in medium containing n-butyrate which blocks histone deacetylation, these newly synthesized histones become acetylated to a far greater extent than do their older homologues. As judged by its increased susceptibility to acetylation, the new chromatin matures at a surprisingly slow rate, the estimated half-time for maturation being about 35 min. Based on this data, we suggest that newly synthesized chromatin is in a relatively extended, accessible conformation, and that it slowly returns to a more compact conformation as it matures.