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Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains

Nature Structural & Molecular Biology volume 20, pages 222–229 (2013)Cite this article

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Abstract

The ISWI family of ATP-dependent chromatin remodelers represses transcription by changing nucleosome positions. ISWI regulates nucleosome positioning by requiring a minimal length of extranucleosomal DNA for moving nucleosomes. ISW2 from Saccharomyces cerevisiae, a member of the ISWI family, has a conserved domain called SLIDE (SANT-like ISWI domain) that binds to extranucleosomal DNA ~19 base pairs from the edge of nucleosomes. Loss of SLIDE binding does not perturb binding of the ATPase domain or the initial movement of DNA inside of nucleosomes. Not only is extranucleosomal DNA required to help recruit ISW2, but also the interactions of the SLIDE domain with extranucleosomal DNA are functionally required to move nucleosomes.

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Figure 1: The SLIDE domain is required for ISW2 complex assembly.
Figure 2: Stable binding of the SLIDE domain to extranucleosomal DNA requires four conserved basic residues in SLIDE.
Figure 3: Binding of mSLIDE to nucleosomes is altered from that of WT.
Figure 4: The SLIDE domain is required for nucleosome movement and ATP hydrolysis.
Figure 5: The SLIDE domain helps move DNA into nucleosomes.
Figure 6: Certain regions in nucleosomal DNA are preferentially altered during remodeling by mSLIDE.
Figure 7: Stable binding of the SLIDE domain promotes the unidirectional movement of DNA exiting nucleosomes in ISW2 remodeling.
Figure 8: The actions of both the DNA translocase and SLIDE domains are required for moving nucleosomes, as shown in this model.

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References

  1. Becker, P.B. & Horz, W. ATP-dependent nucleosome remodeling. Annu. Rev. Biochem. 71, 247–273 (2002).

    Article  CAS  Google Scholar 

  2. Gangaraju, V.K. & Bartholomew, B. Mechanisms of ATP dependent chromatin remodeling. Mutat. Res. 618, 3–17 (2007).

    Article  CAS  Google Scholar 

  3. Clapier, C.R. & Cairns, B.R. The biology of chromatin remodeling complexes. Annu. Rev. Biochem. 78, 273–304 (2009).

    Article  CAS  Google Scholar 

  4. Hota, S.K. & Bartholomew, B. Diversity of operation in ATP-dependent chromatin remodelers. Biochim. Biophys. Acta 1809, 476–487 (2011).

    Article  CAS  Google Scholar 

  5. Zofall, M., Persinger, J. & Bartholomew, B. Functional role of extranucleosomal DNA and the entry site of the nucleosome in chromatin remodeling by ISW2. Mol. Cell. Biol. 24, 10047–10057 (2004).

    Article  CAS  Google Scholar 

  6. Yang, J.G., Madrid, T.S., Sevastopoulos, E. & Narlikar, G.J. The chromatin-remodeling enzyme ACF is an ATP-dependent DNA length sensor that regulates nucleosome spacing. Nat. Struct. Mol. Biol. 13, 1078–1083 (2006).

    Article  CAS  Google Scholar 

  7. Kagalwala, M.N., Glaus, B.J., Dang, W., Zofall, M. & Bartholomew, B. Topography of the ISW2-nucleosome complex: insights into nucleosome spacing and chromatin remodeling. EMBO J. 23, 2092–2104 (2004).

    Article  CAS  Google Scholar 

  8. Stockdale, C., Flaus, A., Ferreira, H. & Owen-Hughes, T. Analysis of nucleosome repositioning by yeast ISWI and Chd1 chromatin remodeling complexes. J. Biol. Chem. 281, 16279–16288 (2006).

    Article  CAS  Google Scholar 

  9. Dang, W., Kagalwala, M.N. & Bartholomew, B. Regulation of ISW2 by concerted action of histone H4 tail and extranucleosomal DNA. Mol. Cell. Biol. 26, 7388–7396 (2006).

    Article  CAS  Google Scholar 

  10. Gangaraju, V.K., Prasad, P., Srour, A., Kagalwala, M.N. & Bartholomew, B. Conformational changes associated with template commitment in ATP-dependent chromatin remodeling by ISW2. Mol. Cell 35, 58–69 (2009).

    Article  CAS  Google Scholar 

  11. Dang, W., Kagalwala, M.N. & Bartholomew, B. The Dpb4 subunit of ISW2 is anchored to extranucleosomal DNA. J. Biol. Chem. 282, 19418–19425 (2007).

    Article  CAS  Google Scholar 

  12. Grüne, T. et al. Crystal structure and functional analysis of a nucleosome recognition module of the remodeling factor ISWI. Mol. Cell 12, 449–460 (2003).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  14. Dang, W. & Bartholomew, B. Domain architecture of the catalytic subunit in the ISW2-nucleosome complex. Mol. Cell. Biol. 27, 8306–8317 (2007).

    Article  CAS  Google Scholar 

  15. Aasland, R., Stewart, A.F. & Gibson, T. The SANT domain: a putative DNA-binding domain in the SWI-SNF and ADA complexes, the transcriptional co-repressor N-CoR and TFIIIB. Trends Biochem. Sci. 21, 87–88 (1996).

    CAS  PubMed  Google Scholar 

  16. Pinskaya, M., Nair, A., Clynes, D., Morillon, A. & Mellor, J. Nucleosome remodeling and transcriptional repression are distinct functions of Isw1 in Saccharomyces cerevisiae. Mol. Cell. Biol. 29, 2419–2430 (2009).

    Article  CAS  Google Scholar 

  17. Eberharter, A., Vetter, I., Ferreira, R. & Becker, P.B. ACF1 improves the effectiveness of nucleosome mobilization by ISWI through PHD-histone contacts. EMBO J. 23, 4029–4039 (2004).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  19. Kassabov, S.R. & Bartholomew, B. Site-directed histone-DNA contact mapping for analysis of nucleosome dynamics. Methods Enzymol. 375, 193–210 (2004).

    Article  CAS  Google Scholar 

  20. Kassabov, S.R., Henry, N.M., Zofall, M., Tsukiyama, T. & Bartholomew, B. High-resolution mapping of changes in histone-DNA contacts of nucleosomes remodeled by ISW2. Mol. Cell. Biol. 22, 7524–7534 (2002).

    Article  CAS  Google Scholar 

  21. Ong, M.S., Richmond, T.J. & Davey, C.A. DNA stretching and extreme kinking in the nucleosome core. J. Mol. Biol. 368, 1067–1074 (2007).

    Article  CAS  Google Scholar 

  22. Richmond, T.J. & Davey, C.A. The structure of DNA in the nucleosome core. Nature 423, 145–150 (2003).

    Article  CAS  Google Scholar 

  23. Luger, K., Mader, A.W., Richmond, R.K., Sargent, D.F. & Richmond, T.J. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389, 251–260 (1997).

    Article  CAS  Google Scholar 

  24. Hall, M.A. et al. High-resolution dynamic mapping of histone-DNA interactions in a nucleosome. Nat. Struct. Mol. Biol. 16, 124–129 (2009).

    Article  CAS  Google Scholar 

  25. Brower-Toland, B.D. et al. Mechanical disruption of individual nucleosomes reveals a reversible multistage release of DNA. Proc. Natl. Acad. Sci. USA 99, 1960–1965 (2002).

    Article  CAS  Google Scholar 

  26. Blosser, T.R., Yang, J.G., Stone, M.D., Narlikar, G.J. & Zhuang, X. Dynamics of nucleosome remodelling by individual ACF complexes. Nature 462, 1022–1027 (2009).

    Article  CAS  Google Scholar 

  27. Dechassa, M.L. et al. SWI/SNF has intrinsic nucleosome disassembly activity that is dependent on adjacent nucleosomes. Mol. Cell 38, 590–602 (2010).

    Article  CAS  Google Scholar 

  28. Shevchuk, N.A. et al. Construction of long DNA molecules using long PCR-based fusion of several fragments simultaneously. Nucleic Acids Res. 32, e19 (2004).

    Article  Google Scholar 

  29. McClelland, M. & Nelson, M. Effect of site-specific methylation on DNA modification methyltransferases and restriction endonucleases. Nucleic Acids Res. 20 (suppl.), 2145–2157 (1992).

    Article  CAS  Google Scholar 

  30. Tsukiyama, T., Palmer, J., Landel, C.C., Shiloach, J. & Wu, C. Characterization of the imitation switch subfamily of ATP-dependent chromatin-remodeling factors in Saccharomyces cerevisiae. Genes Dev. 13, 686–697 (1999).

    Article  CAS  Google Scholar 

  31. Lorch, Y., LaPointe, J.W. & Kornberg, R.D. Nucleosomes inhibit the initiation of transcription but allow chain elongation with the displacement of histones. Cell 49, 203–210 (1987).

    Article  CAS  Google Scholar 

  32. Tullius, T.D., Dombroski, B.A., Churchill, M.E. & Kam, L. Hydroxyl radical footprinting: a high-resolution method for mapping protein-DNA contacts. Methods Enzymol. 155, 537–558 (1987).

    Article  CAS  Google Scholar 

  33. Sengupta, S.M. et al. The interactions of yeast SWI/SNF and RSC with the nucleosome before and after chromatin remodeling. J. Biol. Chem. 276, 12636–12644 (2001).

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank N. Chatterjee for construction of the yeast strain for Isw2 catalytic subunit purification and members of the Bartholomew laboratory for their input. This work was funded by US National Institutes of Health GM 48413 (to B.B.) and the Howard Hughes Medical Institute (to X.Z.). S.D. is supported as a Merck Fellow of the Jane Coffin Childs Memorial Fund for Medical Research.

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  1. Swetansu K Hota and Saurabh K Bhardwaj: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, Illinois, USA

    Swetansu K Hota, Saurabh K Bhardwaj, Yuan-chi Lin & Blaine Bartholomew

  2. Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA

    Sebastian Deindl & Xiaowei Zhuang

  3. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA

    Sebastian Deindl & Xiaowei Zhuang

  4. Department of Physics, Harvard University, Cambridge, Massachusetts, USA

    Xiaowei Zhuang

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  1. Swetansu K Hota
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Contributions

S.K.H., S.K.B., S.D., X.Z. and B.B. designed experiments. S.K.H., S.K.B., S.D. and Y.L. performed experiments. S.K.H., S.D., X.Z. and B.B. wrote the paper.

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Correspondence to Blaine Bartholomew.

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Hota, S., Bhardwaj, S., Deindl, S. et al. Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains. Nat Struct Mol Biol 20, 222–229 (2013). https://doi.org/10.1038/nsmb.2486

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