Article | Published:

Mechanism of chromatin remodelling revealed by the Snf2-nucleosome structure

Nature volume 544, pages 440445 (27 April 2017) | Download Citation

Abstract

Chromatin remodellers are helicase-like, ATP-dependent enzymes that alter chromatin structure and nucleosome positions to allow regulatory proteins access to DNA. Here we report the cryo-electron microscopy structure of chromatin remodeller Switch/sucrose non-fermentable (SWI2/SNF2) from Saccharomyces cerevisiae bound to the nucleosome. The structure shows that the two core domains of Snf2 are realigned upon nucleosome binding, suggesting activation of the enzyme. The core domains contact each other through two induced Brace helices, which are crucial for coupling ATP hydrolysis to chromatin remodelling. Snf2 binds to the phosphate backbones of one DNA gyre of the nucleosome mainly through its helicase motifs within the major domain cleft, suggesting a conserved mechanism of substrate engagement across different remodellers. Snf2 contacts the second DNA gyre via a positively charged surface, providing a mechanism to anchor the remodeller at a fixed position of the nucleosome. Snf2 locally deforms nucleosomal DNA at the site of binding, priming the substrate for the remodelling reaction. Together, these findings provide mechanistic insights into chromatin remodelling.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    & The biology of chromatin remodeling complexes. Annu. Rev. Biochem. 78, 273–304 (2009)

  2. 2.

    , & Mechanisms and functions of ATP-dependent chromatin-remodeling enzymes. Cell 154, 490–503 (2013)

  3. 3.

    , , , & Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389, 251–260 (1997)

  4. 4.

    , & Chromatin remodelling: the industrial revolution of DNA around histones. Nature Rev. Mol. Cell Biol. 7, 437–447 (2006)

  5. 5.

    & ATP-dependent nucleosome remodeling. Annu. Rev. Biochem. 71, 247–273 (2002)

  6. 6.

    , & Nucleosome sliding mechanisms: new twists in a looped history. Nature Struct. Mol. Biol. 20, 1026–1032 (2013)

  7. 7.

    , , , & Structure of chromatin remodeler Swi2/Snf2 in the resting state. Nature Struct. Mol. Biol. 23, 722–729 (2016)

  8. 8.

    , , & The chromodomains of the Chd1 chromatin remodeler regulate DNA access to the ATPase motor. Mol. Cell 39, 711–723 (2010)

  9. 9.

    , , , & Structure and regulation of the chromatin remodeller ISWI. Nature 540, 466–469 (2016)

  10. 10.

    Electron microscopy studies of nucleosome remodelers. Curr. Opin. Struct. Biol. 21, 709–718 (2011)

  11. 11.

    et al. Structural analyses of the chromatin remodelling enzymes INO80-C and SWR-C. Nature Commun. 6, 7108 (2015)

  12. 12.

    et al. Structure and subunit topology of the INO80 chromatin remodeler and its nucleosome complex. Cell 154, 1207–1219 (2013)

  13. 13.

    et al. Molecular architecture of the ATP-dependent chromatin-remodeling complex SWR1. Cell 154, 1220–1231 (2013)

  14. 14.

    et al. Structure and mechanism of the chromatin remodelling factor ISW1a. Nature 472, 448–453 (2011)

  15. 15.

    et al. The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes. Nature 462, 1016–1021 (2009)

  16. 16.

    , , & Structural studies of the human PBAF chromatin-remodeling complex. Structure 13, 267–275 (2005)

  17. 17.

    & New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning. J. Mol. Biol. 276, 19–42 (1998)

  18. 18.

    , , & Chromatin remodeling by ISW2 and SWI/SNF requires DNA translocation inside the nucleosome. Nature Struct. Mol. Biol. 13, 339–346 (2006)

  19. 19.

    et al. Disparity in the DNA translocase domains of SWI/SNF and ISW2. Nucleic Acids Res. 40, 4412–4421 (2012)

  20. 20.

    et al. Architecture of the SWI/SNF-nucleosome complex. Mol. Cell. Biol. 28, 6010–6021 (2008)

  21. 21.

    , , & Structure of RCC1 chromatin factor bound to the nucleosome core particle. Nature 467, 562–566 (2010)

  22. 22.

    et al. Regulation of DNA translocation efficiency within the chromatin remodeler RSC/Sth1 potentiates nucleosome sliding and ejection. Mol. Cell 62, 453–461 (2016)

  23. 23.

    et al. The HSA domain binds nuclear actin-related proteins to regulate chromatin-remodeling ATPases. Nature Struct. Mol. Biol. 15, 469–476 (2008)

  24. 24.

    , , & Swapping function of two chromatin remodeling complexes. Mol. Cell 17, 805–815 (2005)

  25. 25.

    & Regulation of ISWI involves inhibitory modules antagonized by nucleosomal epitopes. Nature 492, 280–284 (2012)

  26. 26.

    , , , & X-ray structures of the Sulfolobus solfataricus SWI2/SNF2 ATPase core and its complex with DNA. Cell 121, 363–373 (2005)

  27. 27.

    & A conserved Swi2/Snf2 ATPase motif couples ATP hydrolysis to chromatin remodeling. Mol. Cell. Biol. 25, 5880–5892 (2005)

  28. 28.

    , & Chromatin remodeling through directional DNA translocation from an internal nucleosomal site. Nature Struct. Mol. Biol. 12, 747–755 (2005)

  29. 29.

    & Three conformational snapshots of the hepatitis C virus NS3 helicase reveal a ratchet translocation mechanism. Proc. Natl Acad. Sci. USA 107, 521–528 (2010)

  30. 30.

    et al. Stepwise nucleosome translocation by RSC remodeling complexes. eLife 5, 5 (2016)

  31. 31.

    & Nucleosome structural studies. Curr. Opin. Struct. Biol. 21, 128–136 (2011)

  32. 32.

    , , & The ATPase domain of ISWI is an autonomous nucleosome remodeling machine. Nature Struct. Mol. Biol. 20, 82–89 (2013)

  33. 33.

    , & DNA stretching and extreme kinking in the nucleosome core. J. Mol. Biol. 368, 1067–1074 (2007)

  34. 34.

    GraFix: stabilization of fragile macromolecular complexes for single particle cryo-EM. Methods Enzymol. 481, 109–126 (2010)

  35. 35.

    , , & Asynchronous data acquisition and on-the-fly analysis of dose fractionated cryoEM images by UCSFImage. J. Struct. Biol. 192, 174–178 (2015)

  36. 36.

    & Accurate determination of local defocus and specimen tilt in electron microscopy. J. Struct. Biol. 142, 334–347 (2003)

  37. 37.

    3-D structures of macromolecules using single-particle analysis in EMAN. Methods Mol. Biol. 673, 157–173 (2010)

  38. 38.

    , , , & Advances in single-particle electron cryomicroscopy structure determination applied to sub-tomogram averaging. Structure 23, 1743–1753 (2015)

  39. 39.

    et al. SPIDER and WEB: processing and visualization of images in 3D electron microscopy and related fields. J. Struct. Biol. 116, 190–199 (1996)

  40. 40.

    et al. Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nature Methods 10, 584–590 (2013)

  41. 41.

    & Prevention of overfitting in cryo-EM structure determination. Nature Methods 9, 853–854 (2012)

  42. 42.

    , , , & Sampling the conformational space of the catalytic subunit of human γ-secretase. eLife 4, 4 (2015)

  43. 43.

    et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004)

  44. 44.

    et al. Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr. D 68, 352–367 (2012)

Download references

Acknowledgements

We thank J. Lei at the Center for Structural Biology (Tsinghua University) and the staff at the Tsinghua University Branch of the National Center for Protein Sciences Beijing for providing facility support. This work was supported by the National Key Research and Development Program to Z.C. (2014CB910100) and to X.L (2016YFA0501102 and 2016YFA0501902), the National Natural Science Foundation of China to Z.C. (31570731, 31270762, 31630046) and to X.L. (31570730), Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, and the ‘Junior One Thousand Talents’ program to Z.C. and X.L.

Author information

Author notes

    • Xiaoyu Liu
    • , Meijing Li
    •  & Xian Xia

    These authors contributed equally to this work.

Affiliations

  1. Ministry of Education Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, China

    • Xiaoyu Liu
    • , Meijing Li
    • , Xian Xia
    • , Xueming Li
    •  & Zhucheng Chen
  2. School of Life Sciences, Tsinghua University, Beijing 100084, China

    • Xiaoyu Liu
    • , Meijing Li
    • , Xian Xia
    • , Xueming Li
    •  & Zhucheng Chen
  3. Tsinghua-Peking Joint Center for Life Sciences, Beijing 100084, China

    • Xiaoyu Liu
    • , Meijing Li
    •  & Xueming Li

Authors

  1. Search for Xiaoyu Liu in:

  2. Search for Meijing Li in:

  3. Search for Xian Xia in:

  4. Search for Xueming Li in:

  5. Search for Zhucheng Chen in:

Contributions

X.Liu and X.X. prepared the proteins and performed the biochemical analyses; M.L. collected the EM data with help from X.Liu and X.X.; M.L. and X.Li performed the EM analysis; Z.C. wrote the manuscript with help from all authors; Z.C. directed and supervised all the research.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Xueming Li or Zhucheng Chen.

Reviewer Information Nature thanks B. Bartholomew, T. Owen-Hughes and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains the uncropped blots.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nature22036

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.