Abstract
ISWI slides nucleosomes along DNA, enabling the structural changes of chromatin required for the regulated use of eukaryotic genomes. Prominent mechanistic models imply cooperation of the ISWI ATPase domain with a C-terminal DNA-binding function residing in the HAND-SANT-SLIDE (HSS) domain. Contrary to these models, we show by quantitative biochemical means that all fundamental aspects of nucleosome remodeling are contained within the compact ATPase module of Drosophila ISWI. This domain can independently associate with DNA and nucleosomes, which in turn activate ATP turnover by inducing a conformational change in the enzyme, and it can autonomously reposition nucleosomes. The role of the HSS domain is to increase the affinity and specificity for nucleosomes. Nucleosome-remodeling enzymes may thus have evolved directly from ancestral helicase-type motors, and peripheral domains have furnished regulatory capabilities that bias the remodeling reaction toward different structural outcomes.
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Acknowledgements
We are grateful to C. Müller (European Molecular Biology Laboratory, Heidelberg, Germany) and D. Rhodes (Nanyang Technological University, Singapore) for the donation of plasmids and to the following colleagues at Ludwig-Maximilians-Universität, Munich, Germany, for materials: N. Hepp for 13-mer nucleosomal arrays, C. Boenisch for 197-bp 601 DNA, V.K. Maier and C. Regnard for recombinant histone octamers. We thank R. Mentele for the Edman digest, I. Forné for performing the LC-MS/MS experiment and Z. Ökten for comments on the manuscript. H.K. acknowledges support by the Elite Network of Bavaria. This work was supported by grants of the Deutsche Forschungsgemeinschaft to P.B.B. (SFB 594 TP A6 and Be 1140/6-1).
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F.M.-P., H.K. and J.L. performed experiments. All authors interpreted results and contributed to writing.
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Mueller-Planitz, F., Klinker, H., Ludwigsen, J. et al. The ATPase domain of ISWI is an autonomous nucleosome remodeling machine. Nat Struct Mol Biol 20, 82–89 (2013). https://doi.org/10.1038/nsmb.2457
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DOI: https://doi.org/10.1038/nsmb.2457
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