Nucleosomes, the basic organizational units of chromatin, package and regulate eukaryotic genomes. ATP-dependent nucleosome-remodeling factors endow chromatin with structural flexibility by promoting assembly or disruption of nucleosomes and the exchange of histone variants. Furthermore, most remodeling factors induce nucleosome movements through sliding of histone octamers on DNA. We summarize recent progress toward unraveling the basic nucleosome sliding mechanism and the interplay of the remodelers' DNA translocases with accessory domains. Such domains optimize and regulate the basic sliding reaction and exploit sliding to achieve diverse structural effects, such as nucleosome positioning or eviction, or the regular spacing of nucleosomes in chromatin.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Nature Communications Open Access 12 April 2019
Nature Communications Open Access 06 April 2018
Actin-related proteins regulate the RSC chromatin remodeler by weakening intramolecular interactions of the Sth1 ATPase
Communications Biology Open Access 22 January 2018
Subscribe to Journal
Get full journal access for 1 year
only $8.25 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Luger, K., Mader, A.W., Richmond, R.K., Sargent, D.F. & Richmond, T.J. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389, 251–260 (1997).
Davey, C.A., Sargent, D.F., Luger, K., Maeder, A.W. & Richmond, T.J. Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 Å resolution. J. Mol. Biol. 319, 1097–1113 (2002).
Flaus, A., Martin, D.M., Barton, G.J. & Owen-Hughes, T. Identification of multiple distinct Snf2 subfamilies with conserved structural motifs. Nucleic Acids Res. 34, 2887–2905 (2006).
Clapier, C.R. & Cairns, B.R. The biology of chromatin remodeling complexes. Annu. Rev. Biochem. 78, 273–304 (2009).
Lorch, Y., Zhang, M. & Kornberg, R.D. Histone octamer transfer by a chromatin-remodeling complex. Cell 96, 389–392 (1999).
Bouazoune, K., Miranda, T.B., Jones, P.A. & Kingston, R.E. Analysis of individual remodeled nucleosomes reveals decreased histone-DNA contacts created by hSWI/SNF. Nucleic Acids Res. 37, 5279–5294 (2009).
Ulyanova, N.P. & Schnitzler, G.R. Human SWI/SNF generates abundant, structurally altered dinucleosomes on polynucleosomal templates. Mol. Cell Biol. 25, 11156–11170 (2005).
Bruno, M. et al. Histone H2A/H2B dimer exchange by ATP-dependent chromatin remodeling activities. Mol. Cell 12, 1599–1606 (2003).
Boeger, H., Griesenbeck, J. & Kornberg, R.D. Nucleosome retention and the stochastic nature of promoter chromatin remodeling for transcription. Cell 133, 716–726 (2008).
Patel, A. et al. Decoupling nucleosome recognition from DNA binding dramatically alters the properties of the Chd1 chromatin remodeler. Nucleic Acids Res. 41, 1637–1648 (2013).Chd1 acquired SWI/SNF-like properties when its DBD was substituted for streptavidin, and the remodeler was targeted to nucleosomes through a biotin tag on histones. This result suggested that binding of the remodeler to linker DNA constrains nucleosome mobility and alters the specificity of the reaction.
Hennig, B.P., Bendrin, K., Zhou, Y. & Fischer, T. Chd1 chromatin remodelers maintain nucleosome organization and repress cryptic transcription. EMBO Rep. 13, 997–1003 (2012).
Yadon, A.N. et al. Chromatin remodeling around nucleosome-free regions leads to repression of noncoding RNA transcription. Mol. Cell Biol. 30, 5110–5122 (2010).
Shim, Y.S. et al. Hrp3 controls nucleosome positioning to suppress non-coding transcription in eu- and heterochromatin. EMBO J. 31, 4375–4387 (2012).
Tirosh, I., Sigal, N. & Barkai, N. Widespread remodeling of mid-coding sequence nucleosomes by Isw1. Genome Biol. 11, R49 (2010).
Cheung, V. et al. Chromatin- and transcription-related factors repress transcription from within coding regions throughout the Saccharomyces cerevisiae genome. PLoS Biol. 6, e277 (2008).
Struhl, K. & Segal, E. Determinants of nucleosome positioning. Nat. Struct. Mol. Biol. 20, 267–273 (2013).
Wippo, C.J. et al. The RSC chromatin remodelling enzyme has a unique role in directing the accurate positioning of nucleosomes. EMBO J. 30, 1277–1288 (2011).
Zhang, Z. et al. A packing mechanism for nucleosome organization reconstituted across a eukaryotic genome. Science 332, 977–980 (2011).
Gkikopoulos, T. et al. A role for Snf2-related nucleosome-spacing enzymes in genome-wide nucleosome organization. Science 333, 1758–1760 (2011).
Pointner, J. et al. CHD1 remodelers regulate nucleosome spacing in vitro and align nucleosomal arrays over gene coding regions in S. pombe. EMBO J. 31, 4388–4403 (2012).
Korber, P. & Becker, P.B. Nucleosome dynamics and epigenetic stability. Essays Biochem. 48, 63–74 (2010).
Badis, G. et al. A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters. Mol. Cell 32, 878–887 (2008).
Fazzio, T.G. & Tsukiyama, T. Chromatin remodeling in vivo: evidence for a nucleosome sliding mechanism. Mol. Cell 12, 1333–1340 (2003).
Whitehouse, I. & Tsukiyama, T. Antagonistic forces that position nucleosomes in vivo. Nat. Struct. Mol. Biol. 13, 633–640 (2006).
Whitehouse, I., Rando, O.J., Delrow, J. & Tsukiyama, T. Chromatin remodelling at promoters suppresses antisense transcription. Nature 450, 1031–1035 (2007).
Liu, N., Peterson, C.L. & Hayes, J.J. SWI/SNF- and RSC-catalyzed nucleosome mobilization requires internal DNA loop translocation within nucleosomes. Mol. Cell Biol. 31, 4165–4175 (2011).
Strohner, R. et al. A 'loop recapture' mechanism for ACF-dependent nucleosome remodeling. Nat. Struct. Mol. Biol. 12, 683–690 (2005).
Längst, G. & Becker, P.B. ISWI induces nucleosome sliding on nicked DNA. Mol. Cell 8, 1085–1092 (2001).
Bowman, G.D. Mechanisms of ATP-dependent nucleosome sliding. Curr. Opin. Struct. Biol. 20, 73–81 (2010).
Zhang, Y. et al. DNA translocation and loop formation mechanism of chromatin remodeling by SWI/SNF and RSC. Mol. Cell 24, 559–568 (2006).
Lia, G. et al. Direct observation of DNA distortion by the RSC complex. Mol. Cell 21, 417–425 (2006).
Aoyagi, S. & Hayes, J.J. hSWI/SNF-catalyzed nucleosome sliding does not occur solely via a twist-diffusion mechanism. Mol. Cell Biol. 22, 7484–7490 (2002).
Aoyagi, S., Wade, P.A. & Hayes, J.J. Nucleosome sliding induced by the xMi-2 complex does not occur exclusively via a simple twist-diffusion mechanism. J. Biol. Chem. 278, 30562–30568 (2003).
Lorch, Y., Davis, B. & Kornberg, R.D. Chromatin remodeling by DNA bending, not twisting. Proc. Natl. Acad. Sci. USA 102, 1329–1332 (2005).
Saha, A., Wittmeyer, J. & Cairns, B.R. Chromatin remodeling by RSC involves ATP-dependent DNA translocation. Genes Dev. 16, 2120–2134 (2002).
Fan, H.Y., He, X., Kingston, R.E. & Narlikar, G.J. Distinct strategies to make nucleosomal DNA accessible. Mol. Cell 11, 1311–1322 (2003).
Whitehouse, I., Stockdale, C., Flaus, A., Szczelkun, M.D. & Owen-Hughes, T. Evidence for DNA translocation by the ISWI chromatin-remodeling enzyme. Mol. Cell Biol. 23, 1935–1945 (2003).
Zofall, M., Persinger, J., Kassabov, S.R. & Bartholomew, B. Chromatin remodeling by ISW2 and SWI/SNF requires DNA translocation inside the nucleosome. Nat. Struct. Mol. Biol. 13, 339–346 (2006).
Saha, A., Wittmeyer, J. & Cairns, B.R. Chromatin remodeling through directional DNA translocation from an internal nucleosomal site. Nat. Struct. Mol. Biol. 12, 747–755 (2005).
Schwanbeck, R., Xiao, H. & Wu, C. Spatial contacts and nucleosome step movements induced by the NURF chromatin remodeling complex. J. Biol. Chem. 279, 39933–39941 (2004).
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).
Dechassa, M.L. et al. Architecture of the SWI/SNF-nucleosome complex. Mol. Cell Biol. 28, 6010–6021 (2008).
Havas, K. et al. Generation of superhelical torsion by ATP-dependent chromatin remodeling activities. Cell 103, 1133–1142 (2000).
Richmond, T.J. & Davey, C.A. The structure of DNA in the nucleosome core. Nature 423, 145–150 (2003).
Tan, S. & Davey, C.A. Nucleosome structural studies. Curr. Opin. Struct. Biol. 21, 128–136 (2011).
Luger, K., Dechassa, M.L. & Tremethick, D.J. New insights into nucleosome and chromatin structure: an ordered state or a disordered affair? Nat. Rev. Mol. Cell Biol. 13, 436–447 (2012).
Mueller-Planitz, F., Klinker, H., Ludwigsen, J. & Becker, P.B. The ATPase domain of ISWI is an autonomous nucleosome remodeling machine. Nat. Struct. Mol. Biol. 20, 82–89 (2013).This quantitative study showed that the ATPase domain of ISWI is an autonomous, rudimentary nucleosome-remodeling machine. It can recognize and remodel nucleosomes, and its ATPase is properly regulated by the nucleosomal substrate.
Clapier, C.R. & Cairns, B.R. Regulation of ISWI involves inhibitory modules antagonized by nucleosomal epitopes. Nature 492, 280–284 (2012).Identified two autoinhibitory modules in the N and C termini of ISWI that regulate the enzyme. These inhibitory structures are released when the remodeler interacts with the histone H4 tail and extranucleosomal DNA.
Clapier, C.R., Langst, G., Corona, D.F., Becker, P.B. & Nightingale, K.P. Critical role for the histone H4 N terminus in nucleosome remodeling by ISWI. Mol. Cell Biol. 21, 875–883 (2001).
Bouazoune, K. & Kingston, R.E. Chromatin remodeling by the CHD7 protein is impaired by mutations that cause human developmental disorders. Proc. Natl. Acad. Sci. USA 109, 19238–19243 (2012).
Hauk, G., McKnight, J.N., Nodelman, I.M. & Bowman, G.D. The chromodomains of the Chd1 chromatin remodeler regulate DNA access to the ATPase motor. Mol. Cell 39, 711–723 (2010).This work presented the crystal structure of Chd1 comprising the NTR and ATPase domain and provided evidence that the NTR regulates the enzyme's ATPase activity by occluding its binding site for nucleic acids.
McKnight, J.N., Jenkins, K.R., Nodelman, I.M., Escobar, T. & Bowman, G.D. Extranucleosomal DNA binding directs nucleosome sliding by Chd1. Mol. Cell Biol. 31, 4746–4759 (2011).Sequence-specific DBDs of unrelated proteins could substitute for the DBD of Chd1, a result suggesting that the DBD and ATPase domains can function as independent modules. Notably, the chimeric remodeler shifted nucleosomes towards and onto the corresponding DNA consensus site.
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).
Ryan, D.P., Sundaramoorthy, R., Martin, D., Singh, V. & Owen-Hughes, T. The DNA-binding domain of the Chd1 chromatin-remodelling enzyme contains SANT and SLIDE domains. EMBO J. 30, 2596–2609 (2011).
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).
Dechassa, M.L. et al. Disparity in the DNA translocase domains of SWI/SNF and ISW2. Nucleic Acids Res. 40, 4412–4421 (2012).
Hall, M.A. et al. High-resolution dynamic mapping of histone-DNA interactions in a nucleosome. Nat. Struct. Mol. Biol. 16, 124–129 (2009).
Hota, S.K. et al. Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains. Nat. Struct. Mol. Biol. 20, 222–229 (2013).Showed that interactions of Isw2 with extranucleosomal DNA promote nucleosome mobilization. The authors resolved several nonsimultaneous structural changes within the nucleosome well before its being shifted to a new DNA location.
Deindl, S. et al. ISWI remodelers slide nucleosomes with coordinated multi-base-pair entry steps and single-base-pair exit steps. Cell 152, 442–452 (2013).Single-molecule fluorescence resonance energy transfer experiments revealed the succession of events during nucleosome sliding by ISWI remodelers in unprecedented detail: the remodelers extruded several base pairs of DNA in single-base-pair increments from the nucleosome before adjacent DNA entered from the opposite end.
Ha, T., Kozlov, A.G. & Lohman, T.M. Single-molecule views of protein movement on single-stranded DNA. Annu. Rev. Biophys. 41, 295–319 (2012).
Lorch, Y., Maier-Davis, B. & Kornberg, R.D. Mechanism of chromatin remodeling. Proc. Natl. Acad. Sci. USA 107, 3458–3462 (2010).
Chaban, Y. et al. Structure of a RSC-nucleosome complex and insights into chromatin remodeling. Nat. Struct. Mol. Biol. 15, 1272–1277 (2008).
Böhm, V. et al. Nucleosome accessibility governed by the dimer/tetramer interface. Nucleic Acids Res. 39, 3093–3102 (2011).
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).
Ryan, D.P. & Owen-Hughes, T. Snf2-family proteins: chromatin remodellers for any occasion. Curr. Opin. Chem. Biol. 15, 649–656 (2011).
Dang, W. & Bartholomew, B. Domain architecture of the catalytic subunit in the ISW2-nucleosome complex. Mol. Cell Biol. 27, 8306–8317 (2007).
Yamada, K. et al. Structure and mechanism of the chromatin remodelling factor ISW1a. Nature 472, 448–453 (2011).
Sen, P. et al. The SnAC domain of SWI/SNF is a histone anchor required for remodeling. Mol. Cell Biol. 33, 360–370 (2013).
Patel, A., McKnight, J.N., Genzor, P. & Bowman, G.D. Identification of residues in Chromodomain helicase dna-binding protein 1 (Chd1) required for coupling atp hydrolysis to nucleosome sliding. J. Biol. Chem. 286, 43984–43993 (2011).
Lewis, R., Durr, H., Hopfner, K.P. & Michaelis, J. Conformational changes of a Swi2/Snf2 ATPase during its mechano-chemical cycle. Nucleic Acids Res. 36, 1881–1890 (2008).
Forne, I., Ludwigsen, J., Imhof, A., Becker, P.B. & Mueller-Planitz, F. Probing the conformation of the ISWI ATPase domain with genetically encoded photoreactive crosslinkers and mass spectrometry. Mol. Cell Proteomics 11, M111 012088 (2012).
Clapier, C.R., Nightingale, K.P. & Becker, P.B. A critical epitope for substrate recognition by the nucleosome remodeling ATPase ISWI. Nucleic Acids Res. 30, 649–655 (2002).
Hamiche, A., Kang, J.G., Dennis, C., Xiao, H. & Wu, C. Histone tails modulate nucleosome mobility and regulate ATP-dependent nucleosome sliding by NURF. Proc. Natl. Acad. Sci. USA 98, 14316–14321 (2001).
Fan, H.Y., Trotter, K.W., Archer, T.K. & Kingston, R.E. Swapping function of two chromatin remodeling complexes. Mol. Cell 17, 805–815 (2005).
Eberharter, A. et al. Acf1, the largest subunit of CHRAC, regulates ISWI-induced nucleosome remodelling. EMBO J. 20, 3781–3788 (2001).
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).
Watson, A.A. et al. The PHD and Chromo domains regulate the ATPase activity of the human chromatin remodeler CHD4. J. Mol. Biol. 422, 3–17 (2012).
He, X., Fan, H.Y., Narlikar, G.J. & Kingston, R.E. Human ACF1 alters the remodeling strategy of SNF2h. J. Biol. Chem. 281, 28636–28647 (2006).
Hargreaves, D.C. & Crabtree, G.R. ATP-dependent chromatin remodeling: genetics, genomics and mechanisms. Cell Res. 21, 396–420 (2011).
Sims, H.I., Lane, J.M., Ulyanova, N.P. & Schnitzler, G.R. Human SWI/SNF drives sequence-directed repositioning of nucleosomes on C-myc promoter DNA minicircles. Biochemistry 46, 11377–11388 (2007).
Rippe, K. et al. DNA sequence- and conformation-directed positioning of nucleosomes by chromatin-remodeling complexes. Proc. Natl. Acad. Sci. USA 104, 15635–15640 (2007).
van Vugt, J.J. et al. Multiple aspects of ATP-dependent nucleosome translocation by RSC and Mi-2 are directed by the underlying DNA sequence. PLoS ONE 4, e6345 (2009).
Floer, M. et al. A RSC/nucleosome complex determines chromatin architecture and facilitates activator binding. Cell 141, 407–418 (2010).
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).
Gangaraju, V.K. & Bartholomew, B. Dependency of ISW1a chromatin remodeling on extranucleosomal DNA. Mol. Cell Biol. 27, 3217–3225 (2007).
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).
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).
Zentner, G.E., Tsukiyama, T. & Henikoff, S. ISWI and CHD chromatin remodelers bind promoters but act in gene bodies. PLoS Genet. 9, e1003317 (2013).
Gossett, A.J. & Lieb, J.D. In vivo effects of histone H3 depletion on nucleosome occupancy and position in Saccharomyces cerevisiae. PLoS Genet. 8, e1002771 (2012).
Dechassa, M.L. et al. SWI/SNF has intrinsic nucleosome disassembly activity that is dependent on adjacent nucleosomes. Mol. Cell 38, 590–602 (2010).
Ballaré, C. et al. Nucleosome-driven transcription factor binding and gene regulation. Mol. Cell 49, 67–79 (2013).
Engeholm, M. et al. Nucleosomes can invade DNA territories occupied by their neighbors. Nat. Struct. Mol. Biol. 16, 151–158 (2009).
Lorch, Y., Griesenbeck, J., Boeger, H., Maier-Davis, B. & Kornberg, R.D. Selective removal of promoter nucleosomes by the RSC chromatin-remodeling complex. Nat. Struct. Mol. Biol. 18, 881–885 (2011).
Racki, L.R. et al. The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes. Nature 462, 1016–1021 (2009).
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).
Lusser, A., Urwin, D.L. & Kadonaga, J.T. Distinct activities of CHD1 and ACF in ATP-dependent chromatin assembly. Nat. Struct. Mol. Biol. 12, 160–166 (2005).
Work on nucleosome remodeling in the laboratories of F.M.-P. and P.B.B. is supported by the Deutsche Forschungsgemeinschaft through SFB 594 as well as grants MU3613/1-1, BE1140/6 and BE1140/7.
The authors declare no competing financial interests.
About this article
Cite this article
Mueller-Planitz, F., Klinker, H. & Becker, P. Nucleosome sliding mechanisms: new twists in a looped history. Nat Struct Mol Biol 20, 1026–1032 (2013). https://doi.org/10.1038/nsmb.2648
This article is cited by
Nature Communications (2019)
Nature Structural & Molecular Biology (2019)
Actin-related proteins regulate the RSC chromatin remodeler by weakening intramolecular interactions of the Sth1 ATPase
Communications Biology (2018)
Nature Communications (2018)