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Nucleosome–Chd1 structure and implications for chromatin remodelling


Chromatin-remodelling factors change nucleosome positioning and facilitate DNA transcription, replication, and repair1. The conserved remodelling factor chromodomain-helicase-DNA binding protein 1(Chd1)2 can shift nucleosomes and induce regular nucleosome spacing3,4,5. Chd1 is required for the passage of RNA polymerase IIthrough nucleosomes6 and for cellular pluripotency7. Chd1 contains the DNA-binding domains SANT and SLIDE, a bilobal motor domain that hydrolyses ATP, and a regulatory double chromodomain. Here we report the cryo-electron microscopy structure of Chd1 from the yeast Saccharomyces cerevisiae bound to a nucleosome at a resolution of 4.8 Å. Chd1 detaches two turns of DNA from the histone octamer and binds between the two DNA gyres in a state poised for catalysis. The SANT and SLIDE domains contact detached DNA around superhelical location (SHL) −7 of the first DNA gyre. The ATPase motor binds the second DNA gyre at SHL +2 and is anchored to the N-terminal tail of histone H4, as seen in a recent nucleosome–Snf2 ATPase structure8. Comparisons with published results9 reveal that the double chromodomain swings towards nucleosomal DNA at SHL +1, resulting in ATPase closure. The ATPase can then promote translocation of DNA towards the nucleosome dyad, thereby loosening the first DNA gyre and remodelling the nucleosome. Translocation may involve ratcheting of the two lobes of the ATPase, which is trapped in a pre- or post-translocation state in the absence8 or presence, respectively, of transition state-mimicking compounds.

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Figure 1: Structure of nucleosome–Chd1 complex.
Figure 2: Chd1–DNA interactions.
Figure 3: Chd1 structural changes and ATPase activation.

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We thank past and present members of the Cramer laboratory including F. Fischer, R. Kohler, S. Neyer, D. Tegunov, and Y. Xu. We thank the members of the Halic laboratory for Xenopus laevis histone expression plasmids, a plasmid containing the Widom 601 sequence and initial advice on histone purification. S.M.V. was supported by an EMBO Long-Term-Fellowship (ALTF 745-2014). P.C. was supported by the Deutsche Forschungsgemeinschaft (SFB860, SPP1935), the European Research Council Advanced Investigator Grant TRANSREGULON (grant agreement No. 693023), and the Volkswagen Foundation.

Author information

Authors and Affiliations



L.F. designed and carried out experiments and performed cryo-EM data acquisition and analysis. S.M.V. developed the protein expression strategy, performed baculovirus production, and insect cell expression. C.W. assisted with cryo-EM grid preparation and data collection. P.C. designed and supervised research. L.F. and P.C. interpreted the data and wrote the manuscript, with input from all authors.

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Correspondence to Patrick Cramer.

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Extended data figures and tables

Extended Data Figure 1 Cryo-EM structure determination and analysis.

a, Formation of the nucleosome–Chd1–FACT–Paf1C complex. SDS–PAGE of peak fraction used for cryo-EM grid preparation containing Chd1, FACT subunits, Paf1C subunits, and histones. The identity of the bands was confirmed by mass spectrometry. For gel source data, see Supplementary Fig. 1. b, Representative cryo-EM micrograph of data collection. c, 2D class averages contain nucleosome-like shapes. d, Sorting and classification tree used to reconstruct the nucleosome–Chd1 particle at 4.8 Å resolution. Steps 1 and 2 of batch 1 global classification are shown representatively for all three batches.

Extended Data Figure 2 Quality of the nucleosome–Chd1 structure.

a, Overall fit of the nucleosome–Chd1 structure to the electron density. Two views are depicted as in Fig. 1b, c. b–f, Electron density (grey mesh) for various Chd1 domains reveals secondary structure and a good fit for DNA (SHL −4 to SHL +7). g, Superposition of the histone octamer core with canonical octamer core (PDB code 3LZ0). The canonical octamer core is rendered in grey. h, Nucleosome–Chd1 reconstruction coloured according to local resolution43. i, Angular distribution of particles. Red dots indicate the presence of at least one particle image assigned within ±1°. Shading from white to black indicates the density of particle images at a given orientation. j, Estimation of the average resolution. The dark blue line indicates the Fourier shell correlation (FSC) between the half maps of the reconstruction. The dotted light blue line indicates the Fourier shell correlation between the derived model and the reconstruction. Resolutions are given for the FSC 0.143 and the FSC 0.5 criteria. The dotted lines show the Fourier shell correlation between the derived Chd1 domains and the corresponding masked regions.

Extended Data Figure 3 Chd1–DNA interactions and Chd1 interaction interfaces.

a, Overview of Chd1–DNA interactions. b, Contact of chromo-wedge with DNA at SHL +1. c, Secondary DNA contacts of ATPase. Contact of motif Ib with first DNA gyre around SHL −6. d, Modelling linear B-DNA (orange) onto the ATPase motor in the nucleosome–Chd1 structure leads to a clash with the double chromodomain (purple). B-DNA was superimposed onto nucleosomal DNA at SHL +2. e, ADP·BeF3 binds in the active site of the Chd1 ATPase motor. Electron density is shown for ADP·BeF3, motif I (Walker A, P-loop, residues 403–410), motif II (Walker B, residues 510–515), and the arginine fingers (R804 and R807). Motifs I and II are shown in ribbon representation. ADP·BeF3 and the arginine finger residues are shown as sticks. The density for ADP is strong, whereas the density for BeF3 is weaker and thus we cannot formally rule out that BeF3 is not bound or shows only partial occupancy. f, Contact of W793 with the phosphate backbone of the guide strand at SHL +2. Electron density is shown as a grey mesh. Side chain of W793 is shown as a stick representation. g, Interface between the double chromodomain and the SANT and SLIDE domains of the DNA binding region. Chd1 domains are coloured as in Fig. 1a. h, Sequence of the Widom 601 sequence with 63 bp of extranucleosomal DNA.

Extended Data Figure 4 ATPase conservation and histone H4 tail binding.

a, Chd1 binds the N-terminal tail of histone H4 (green) with ATPase lobe 2 (surface representation coloured according to electrostatic surface potential; red, negative; white, neutral; blue, positive). The view is the inverse of that in Fig. 1b (that is, after a 180° rotation). b, Chd1 ATPase activity results in DNA translocation towards the octamer dyad, loosening DNA gyre 1 and triggering nucleosome remodelling. c, Sequence alignment of ATPase regions in S. cerevisiae (Sc) Chd1 (356–883), ScIsw1 (177–689), ScSnf2 (746–1270), Homo sapiens (Hs) Chd4 (703–1233), Drosophila melanogaster (Dm) Mi-2 (707–1231), and Sulfolobus solfataricus (Sso) Rad54 (423–802). Arginine ‘fingers’ of ScChd1 (R804 and R807) are indicated and ATPase motifs are underlined. Sequence coloured according to identity. Darker shades of blue indicate higher conservation, whereas lighter shades of blue indicate less conservation. Alignment was generated with MAFFT51 and visualized using JalView52.

Extended Data Table 1 Cryo-EM data collection, refinement, and validation statistics

Supplementary information

Supplementary Figure 1

This file contains the uncropped scan with size marker indication. The region presented in Extended Data Figure 1a is indicated by rectangle with dashed lines. (PDF 236 kb)

Reporting Summary (PDF 71 kb)

Overview of the nucleosome-Chd1 structure

A 3D overview of the nucleosome-Chd1 structure fitted into the cryo-EM electron density. (MOV 13340 kb)

Structural changes and ATPase activation

The video first shows DNA detachment, then swinging of the double chromodomain onto nucleosomal DNA, and then ATPase closure. (MP4 15262 kb)

Model for DNA translocation by the Chd1 ATPase motor

The video shows a model for DNA translocation by the Chd1 ATPase motor on B-DNA. For details see text. (MP4 7238 kb)

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Farnung, L., Vos, S., Wigge, C. et al. Nucleosome–Chd1 structure and implications for chromatin remodelling. Nature 550, 539–542 (2017).

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