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Structure of a RSC–nucleosome complex and insights into chromatin remodeling

Abstract

ATP-dependent chromatin-remodeling complexes, such as RSC, can reposition, evict or restructure nucleosomes. A structure of a RSC–nucleosome complex with a nucleosome determined by cryo-EM shows the nucleosome bound in a central RSC cavity. Extensive interaction of RSC with histones and DNA seems to destabilize the nucleosome and lead to an overall ATP-independent rearrangement of its structure. Nucleosomal DNA appears disordered and largely free to bulge out into solution as required for remodeling, but the structure of the RSC–nucleosome complex indicates that RSC is unlikely to displace the octamer from the nucleosome to which it is bound. Consideration of the RSC–nucleosome structure and published biochemical information suggests that ATP-dependent DNA translocation by RSC may result in the eviction of histone octamers from adjacent nucleosomes.

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Figure 1: Cryo-EM RSC data and reconstruction of the RSC complex.
Figure 2: Statistical analysis of domain mobility in the RSC complex.
Figure 3: Cryo-EM analysis of the RSC–nucleosome complex.
Figure 4: Analysis of the density in the central cavity of the RSC–nucleosome reconstruction and comparison with the X-ray structure of the nucleosome.

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Author information

Authors and Affiliations

Authors

Contributions

B.M.-D. purified RSC and nucleosomes; Y.L. established optimal conditions and determined affinity for RSC–nucleosome interaction; C.E. and W.-H.C. worked on the initial RSC and RSC–nucleosome cryo–reconstructions; F.Z. collected a portion of the RSC cryo-EM data; Y.C. collected additional cryo-EM data and was responsible for refinement and analysis of the final cryo-EM reconstructions; R.D.K. and F.J.A. interpreted the results and wrote the manuscript.

Corresponding author

Correspondence to Francisco J Asturias.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6 and Supplementary Methods (PDF 322 kb)

Supplementary Movie 1

Cryo-EM reconstruction of the RSC chromatin remodeling complex. (MOV 556 kb)

Supplementary Movie 2

RSC bottom domain movement viewed from the position close to the front view. (MOV 136 kb)

Supplementary Movie 3

Cryo-EM reconstruction of the RSC-nucleosome complex and comparison with the reconstruction of RSC alone. (MOV 1032 kb)

Supplementary Movie 4

Docking of a model of the histones into the central portion of the density apparent in the RSC-nucleosome reconstruction. (MOV 7913 kb)

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Chaban, Y., Ezeokonkwo, C., Chung, WH. et al. Structure of a RSC–nucleosome complex and insights into chromatin remodeling. Nat Struct Mol Biol 15, 1272–1277 (2008). https://doi.org/10.1038/nsmb.1524

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