During chromatin replication and nucleosome assembly, newly synthesized histone 
H4 is acetylated before it is deposited onto DNA, then deacetylated as assembly 
proceeds. In a previous study (Perry and Annunziato, Nucleic Acids Res. 17, 4275 
[1989]) it was shown that when replication occurs in the presence of sodium 
butyrate (thereby inhibiting histone deacetylation), nascent chromatin fails to 
mature fully and instead remains preferentially sensitive to DNaseI, more 
soluble in magnesium, and depleted of histone H1 (relative to mature chromatin). 
In the following report the relationships between chromatin replication, histone 
acetylation, and H1-mediated nucleosome aggregation were further investigated. 
Chromatin was replicated in the presence or absence of sodium butyrate; isolated 
nucleosomes were stripped of linker histone, reconstituted with H1, and treated 
to produce Mg(2+)-soluble and Mg(2+)-insoluble chromatin fractions. Following 
the removal of H1, all solubility differences between chromatin replicated in 
sodium butyrate for 30 min (bu-chromatin) and control chromatin were lost. 
Reconstitution with H1 completely restored the preferential Mg(2+)-solubility of 
bu-chromatin, demonstrating that a reduced capacity for aggregation/condensation 
is an inherent feature of acetylated nascent nucleosomes; however, titration 
with excess H1 caused the solubility differences to be lost again. Moreover, 
when the core histone N-terminal "tails" (the sites of acetylation) were removed 
by trypsinization prior to reconstitution, H1 was unable to reestablish the 
altered solubility of chromatin replicated in butyrate. Thus, the core histone 
"tails," and the acetylation thereof, not only modulate H1-mediated nucleosome 
interactions in vitro, but also strongly influence the ability of H1 to 
differentiate between new and old nucleosomes. The data suggest a possible 
mechanism for the control of H1 deposition and/or chromatin folding during 
nucleosome assembly.