Patterns of histone acetylation

Abstract

The N-terminal domains of all four core histones are subject to reversible acetylation at certain lysine residues. This modification has been functionally linked to transcription, histone deposition at replication and to histone removal during spermatogenesis. To increase understanding of the significance of this modification we have studied the specificity of site utilisation in the monoacetyl, diacetyl and triacetyl forms of histones H3, H4 and H2B (histone H2A has only a single modification site), using pig thymus and HeLa cells as the source of histones. The HeLa histones were extracted from cells grown both with and without butyrate treatment. It is found that for histone H3 there is a fairly strict order of site occupancy: Lysl4, followed by Lys23, followed by Lysl8 in both pig and HeLa histones. Since the order and specificity is the same when butyrate is added to the HeLa cell cultures, we conclude that addition of the fatty acid does not scramble the specificity of site utilisation, but merely allows more of the natural forms of modified histone to accumulate. For histone H4, the monoacetyl form is exclusively modified at Lysl6, but further addition of acetyl groups is less specific and progresses through sites 12, 8 and 5 in an N-terminal direction. Similar results were obtained for H4 from both pig thymus and butyratetreated HeLa cells. Histone H2B could be studied in detail only from butyrate-treated HeLa cells and a much lower level of site specificity was found: sites 12 and 15 were preferred to the more N-and C-terminal sites at Lys5 and Lys20. The data reinforces the view that lysine acetylation in core histones is a very specific phenomenon that plays several functionally distinct roles. The high degree of site specificity makes it unlikely that the structural effects of acetylation are mediated merely by a generalised reduction of charge in the histone N-terminal domains.

Acetylation of RTN-1C regulates the induction of ER stress by the inhibition of HDAC activity in neuroectodermal tumors

“…In particular, lysine 16, located in a very basic region in the N-terminus of histone H4 (amino acids 14-18), has been shown to be important for DNA binding and activation of chromatin (Thorne et al, 1990). As this region includes the KRH domain identical to that found in RTN1, we wondered whether RTN-1C might be modified by acetylation.…”

Cross-talk between Histone Modifications in Response to Histone Deacetylase Inhibitors

“…The magnitude of the response varies with the acetyl isoform examined, from an ϳ8-fold increase in H4K8ac to an ϳ24-fold increase in H3K9/ K18ac (Fig. 1, A and B), reflecting the abundance of these histone acetyl isoforms in untreated cells and the differing rates of acetyl turnover at different lysine residues (21). HDAC inhibitors also induce a concomitant increase in methylation at H3K4, the degree of enhancement depending on the specific methyl isoform; H3K4me3 increases ϳ5-fold and H3K4me2 levels increase ϳ3-fold, whereas H3K4me1 levels show only a small increase (1.5 to 2-fold, Fig.…”

Identification of a conserved erythroid specific domain of histone acetylation across the α-globin gene cluster

“…Does this represent a specific acetylation of Lys-5 or does it more simply reflect the overall level of histone acetylation? In general, the N-terminal lysines in H4 are acetylated in a defined order: Lys-16 followed by Lys-8 and -12, with Lys-5 being acetylated last (39). A simple increase in acetylation of all terminal lysines moving the equilibrium toward the tetra-acetylated form would certainly result in enrichment of Lys-5.…”