Abstract
BackgroundThe tight organisation of eukaryotic genomes as chromatin hinders the interaction of many DNA-binding regulators. The local accessibility of DNA is regulated by many chromatin modifying enzymes, among them the nucleosome remodelling factors. These enzymes couple the hydrolysis of ATP to disruption of histone-DNA interactions, which may lead to partial or complete disassembly of nucleosomes or their sliding on DNA. The diversity of nucleosome remodelling factors is reflected by a multitude of ATPase complexes with distinct subunit composition.ResultsWe found further diversification of remodelling factors by posttranslational modification. The histone acetyltransferase GCN5 can acetylate the Drosophila remodelling ATPase ISWI at a single, conserved lysine, K753, in vivo and in vitro. The target sequence is strikingly similar to the N-terminus of histone H3, where the corresponding lysine, H3K14, can also be acetylated by GCN5. The acetylated form of ISWI represents a minor species presumably associated with the nucleosome remodelling factor NURF.ConclusionAcetylation of histone H3 and ISWI by GCN5 is explained by the sequence similarity between the histone and ISWI around the acetylation site. The common motif RKT/SxGx(Kac)xPR/K differs from the previously suggested GCN5/PCAF recognition motif GKxxP. This raises the possibility of co-regulation of a nucleosome remodelling factor and its nucleosome substrate through acetylation of related epitopes and suggests a direct crosstalk between two distinct nucleosome modification principles.
Highlights
The tight organisation of eukaryotic genomes as chromatin hinders the interaction of many DNA-binding regulators
We found that Drosophila ISWI, the founding member of a family of nucleosome remodelling ATPases, was preferentially acetylated by GCN5 at a single lysine within a amino acid sequence of high similarity to the N-terminus of histone H3
In the absence of Trichostatin A (TSA) ISWI was barely detectable in the αAcLysine precipitate, which may be due to the inefficiency of the antibody and/or the small amounts of acetylated ISWI present in Kc cells (Figure 1B, lanes 3–5)
Summary
The tight organisation of eukaryotic genomes as chromatin hinders the interaction of many DNA-binding regulators. Disruption of DNA-histone interactions by nucleosome remodelling ATPases may lead to a variety of transitions of chromatin structure, such as the partial or complete disassembly of nucleosomes, the exchange of histones, or the sliding of intact histone octamers on DNA [1,2,3,4] In many cases their activity is focused on local disruption of the nucleosomal fibre through recruitment of DNA-binding regulators to promote access of factors further downstream in the cascade of events that leads to promoter opening [2]. Such a role has been suggested for the SWI2/SNF2-type ATPase hBRM by the early finding that its expression is down-regulated when cells receive a mitogenic stimulus or during ras-mediated oncogenic transformation, whereas its forced expression partially reverses transformation [8]
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