Abstract
ISWI is the catalytic subunit of several ATP-dependent chromatin remodelling factors that catalyse the sliding of nucleosomes along DNA and thereby endow chromatin with structural flexibility. Full activity of ISWI requires residues of a basic patch of amino acids in the N-terminal ‘tail’ of histone H4. Previous studies employing oligopeptides and mononucleosomes suggested that acetylation of the H4 tail at lysine 16 (H4K16) within the basic patch may inhibit the activity of ISWI. On the other hand, the acetylation of H4K16 is known to decompact chromatin fibres. Conceivably, decompaction may enhance the accessibility of nucleosomal DNA and the H4 tail for ISWI interactions. Such an effect can only be evaluated at the level of nucleosome arrays. We probed the influence of H4K16 acetylation on the ATPase and nucleosome sliding activity of Drosophila ISWI in the context of defined, in vitro reconstituted chromatin fibres with physiological nucleosome spacing and linker histone content. Contrary to widespread expectations, the acetylation did not inhibit ISWI activity, but rather stimulated ISWI remodelling under certain conditions. Therefore, the effect of H4K16 acetylation on ISWI remodelling depends on the precise nature of the substrate.
Highlights
The nucleosomal organisation of genomic DNA constitutes a barrier to DNA binding factors
ISWI regulation by H4K16ac It is firmly established that the H4 tail plays a crucial role in the nucleosome sliding mechanism of ISWI [5,6]
A recent study provided mechanistic insights by identifying a peptide motif in the N-terminus of ISWI (AutoN) that resembles the basic patch of histone H4 [54]
Summary
The nucleosomal organisation of genomic DNA constitutes a barrier to DNA binding factors. Of key importance in these processes are chromatin remodelling factors, a conserved class of enzymes that utilize the energy from ATP hydrolysis to reposition, evict, and assemble nucleosomes [1,2]. ISWI, a prominent member of this class of ‘remodelling’ ATPases, is the catalytic subunit of several different chromatin remodelling complexes [3,4]. All ISWI complexes investigated to date mobilize nucleosomes by repositioning histone octamers along DNA in a process termed ‘nucleosome sliding’ [5,6]. ISWI complexes are involved in multiple essential nuclear processes, such as transcription regulation, DNA repair, and the maintenance of chromatin higher order structure [13,14]. How ISWI complexes are targeted and regulated and how their biochemical properties are translated into various biological outcomes remains largely elusive
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