Site-specific acetylation of ISWI by GCN5.
BACKGROUND
The 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.


RESULTS
We 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.


CONCLUSIONS
Acetylation 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.
Ferreira
Roger
R
Adolf-Butenandt-Institut, Molekularbiologie, 80336 München, Germany. rferreira@epo.org
Eberharter
Anton
A
Bonaldi
Tiziana
T
Chioda
Mariacristina
M
Imhof
Axel
A
Becker
Peter B
PB
D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D006690:Bisbenzimidazole / Q000378:metabolism; D002460:Cell Line; D004330:Drosophila / Q000166:cytology / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism; D017353:Gene Deletion; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
D000251:Adenosine Triphosphatases; D006690:Bisbenzimidazole; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D051548:Histone Acetyltransferases; D006877:Hydroxamic Acids; D008239:Lysine; D011994:Recombinant Proteins; D014157:Transcription Factors; C086468:ISWI protein; C012589:trichostatin A; C470557:GCN5 protein, Drosophila; D000099224:p300-CBP-Associated Factor