Core histone acetylation is regulated by linker histone stoichiometry in vivo

We investigated the relationship between linker histone stoichiometry and t he acetylation of core histones in vivo. Exponentially growing cell lines i nduced to overproduce either of two H1 variants, H1(0) or H1c, displayed si gnificantly reduced rates of incorporation of [H-3]acetate into all four co re histones. Pulse-chase experiments indicated that the rates of histone de acetylation were similar in all cell lines. These effects were also observe d in nuclei isolated from these cells upon labeling with [H-3]acetyl-CoA. N uclear extracts prepared from control and H1-overexpressing cell lines disp layed similar levels of histone acetylation activity on chromatin templates prepared from control cells, In contrast, extracts prepared from control c ells were significantly less active on chromatin templates prepared from H1 -overexpressing cells than on templates prepared from control cells. Reduce d levels of acetylation in H1-overproducing cell lines do not appear to dep end on higher order chromatin structure, because it persists even after dig estion of the chromatin with micrococcal nuclease, The results suggest that alterations in chromatin structure, resulting from changes in linker histo ne stoichiometry may modulate the levels or rates of core histone acetylati on in vivo.