Abstract
We investigated the relationship between linker histone stoichiometry and the acetylation of core histones in vivo. Exponentially growing cell lines induced to overproduce either of two H1 variants, H1(0) or H1c, displayed significantly reduced rates of incorporation of [(3)H]acetate into all four core histones. Pulse-chase experiments indicated that the rates of histone deacetylation were similar in all cell lines. These effects were also observed in nuclei isolated from these cells upon labeling with [(3)H]acetyl-CoA. Nuclear extracts prepared from control and H1-overexpressing cell lines displayed similar levels of histone acetylation activity on chromatin templates prepared from control cells. In contrast, extracts prepared from control cells were significantly less active on chromatin templates prepared from H1-overexpressing cells than on templates prepared from control cells. Reduced levels of acetylation in H1-overproducing cell lines do not appear to depend on higher order chromatin structure, because it persists even after digestion of the chromatin with micrococcal nuclease. The results suggest that alterations in chromatin structure, resulting from changes in linker histone stoichiometry may modulate the levels or rates of core histone acetylation in vivo.
Highlights
Core Histone Acetylation Is Regulated by Linker Histone Stoichiometry in Vivo*We investigated the relationship between linker histone stoichiometry and the acetylation of core histones in vivo
The relationship between histone hyperacetylation and transcriptionally active chromatin was made many years ago [7, 8]
Silent chromatin is often hypoacetylated and histone deacetylases (HDACs) have been shown to be components of transcriptional corepressors and silencers that are targeted to the appropriate DNA sequences [11, 12]
Summary
We investigated the relationship between linker histone stoichiometry and the acetylation of core histones in vivo. The results suggest that alterations in chromatin structure, resulting from changes in linker histone stoichiometry may modulate the levels or rates of core histone acetylation in vivo. Several recent reports provide direct evidence that the acetylation status of nucleosomal core histones has a causal relationship to gene activity [13,14,15,16]. Linker histone-dependent transcriptional repression was not affected by the acetylation state of the core histones [42]. A recent report demonstrated that the linker histones H1 and H5 inhibit the acetylation of mononucleosomes and oligonucleosomes by the histone acetyltransferase activity of p300/CBPassociated factor (PCAF) in vitro [45]. Values were estimated as previously described [17] and are the mean Ϯ S.D. from four separate experiments
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