Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Chromatin remodelling: the industrial revolution of DNA around histones

Key Points

  • Chromatin-remodelling machines (remodellers) are large, multi-protein complexes that use the energy of ATP hydrolysis to mobilize and restructure nucleosomes. Nucleosomes wrap 146 bp of DNA in 1.7 turns around a histone-octamer disk, and the DNA inside the nucleosome is generally inaccessible to DNA-binding factors. Remodellers provide access to the underlying DNA to enable transcription, chromatin assembly, DNA repair and other processes. Central questions in the chromatin field include how remodellers convert the energy of ATP hydrolysis into a mechanical force to mobilize the nucleosome, and how different remodeller complexes select which nucleosome to move and restructure.

  • Remodellers are partitioned into five families with specialized biological roles. However, all remodellers contain a subunit with a conserved ATPase domain. As well as the conserved ATPase, each remodeller complex contains unique proteins that specialize each remodeller for these biological roles. However, as all remodellers move nucleosomes, and as all movement is ATP dependent, mobilization is probably a property of the conserved ATPase subunit.

  • The ATPase domains of remodellers are similar in sequence and structure to known DNA-translocating proteins in viruses and bacteria. Recent evidence with the SWI/SNF and ISWI remodeller families has revealed that remodeller ATPases are directional DNA translocases that are capable of the directional pumping of DNA. This property is applied to nucleosomes in the following manner: the ATPase seems to bind 40 bp inside the nucleosome, from which location it pumps DNA around the histone-octamer surface. This enables the movement of the nucleosome along the DNA, allowing the exposure of DNA to regulatory factors.

  • The additional domains and proteins that are attached to the ATPase are important for nucleosome selection, and additionally help to regulate the ATPase activity. These attendant proteins bind to histones and nucleosomal DNA, and their binding to these epitopes is affected by the histone-modification state. Therefore, the modification state of histones helps to determine whether the nucleosome is an appropriate substrate for a remodeller complex.

Abstract

Chromatin remodellers are specialized multi-protein machines that enable access to nucleosomal DNA by altering the structure, composition and positioning of nucleosomes. All remodellers have a catalytic ATPase subunit that is similar to known DNA-translocating motor proteins, suggesting DNA translocation as a unifying aspect of their mechanism. Here, we explore the diversity and specialization of chromatin remodellers, discuss how nucleosome modifications regulate remodeller activity and consider a model for the exposure of nucleosomal DNA that involves the use of directional DNA translocation to pump 'DNA waves' around the nucleosome.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Dynamic properties of nucleosomes.
Figure 2: Composition of SWI/SNF and ISWI remodelling complexes.
Figure 3: Sliding properties of SWI/SNF and ISWI remodelling complexes.
Figure 4: The wave?ratchet?wave model for DNA translocation.

References

  1. Kornberg, R. D. & Lorch, Y. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98, 285?294 (1999).

    CAS  PubMed  Article  Google Scholar 

  2. Jenuwein, T. & Allis, C. D. Translating the histone code. Science 293, 1074?1080 (2001).

    CAS  PubMed  Article  Google Scholar 

  3. Strahl, B. D. & Allis, C. D. The language of covalent histone modifications. Nature 403, 41?45 (2000).

    CAS  Article  PubMed  Google Scholar 

  4. Owen-Hughes, T. Colworth memorial lecture. Pathways for remodelling chromatin. Biochem. Soc. Trans. 31, 893?905 (2003).

    CAS  PubMed  Article  Google Scholar 

  5. Cosma, M. P., Tanaka, T. & Nasmyth, K. Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle- and developmentally regulated promoter. Cell 97, 299?311 (1999).

    CAS  Article  PubMed  Google Scholar 

  6. Fan, H. Y., He, X., Kingston, R. E. & Narlikar, G. J. Distinct strategies to make nucleosomal DNA accessible. Mol. Cell 11, 1311?1322 (2003).

    CAS  PubMed  Article  Google Scholar 

  7. Saha, A., Wittmeyer, J. & Cairns, B. R. Chromatin remodeling by RSC involves ATP-dependent DNA translocation. Genes Dev. 16, 2120?2134 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  8. Jaskelioff, M., Van Komen, S., Krebs, J. E., Sung, P. & Peterson, C. L. Rad54p is a chromatin remodeling enzyme required for heteroduplex DNA joint formation with chromatin. J. Biol. Chem. 278, 9212?9218 (2003).

    CAS  PubMed  Article  Google Scholar 

  9. 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). References 7?9 provide biochemical evidence for DNA translocation by the SWI/SNF and the ISWI family of remodellers.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  10. Alexeev, A., Mazin, A. & Kowalczykowski, S. C. Rad54 protein possesses chromatin-remodeling activity stimulated by the Rad51?ssDNA nucleoprotein filament. Nature Struct. Biol. 10, 182?186 (2003).

    CAS  PubMed  Article  Google Scholar 

  11. Durr, H., Korner, C., Muller, M., Hickmann, V. & Hopfner, K. P. X-ray structures of the Sulfolobus solfataricus SWI2/SNF2 ATPase core and its complex with DNA. Cell 121, 363?373 (2005). This study, along with reference 60, provides structural evidence for Rad54 as a DNA-translocating enzyme.

    PubMed  Article  CAS  Google Scholar 

  12. 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).

    CAS  Article  PubMed  Google Scholar 

  13. Henikoff, S., Furuyama, T. & Ahmad, K. Histone variants, nucleosome assembly and epigenetic inheritance. Trends Genet. 20, 320?326 (2004).

    CAS  Article  PubMed  Google Scholar 

  14. Mizuguchi, G. et al. ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex. Science 303, 343?348 (2004).

    CAS  PubMed  Article  Google Scholar 

  15. Smith, M. M. Centromeres and variant histones: what, where, when and why? Curr. Opin. Cell Biol. 14, 279?285 (2002).

    CAS  PubMed  Article  Google Scholar 

  16. Ahmad, K. & Henikoff, S. Histone H3 variants specify modes of chromatin assembly. Proc. Natl Acad. Sci. USA 99 (Suppl. 4), 16477?16484 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Krogan, N. J. et al. A Snf2 family ATPase complex required for recruitment of the histone H2A variant Htz1. Mol. Cell 12, 1565?1576 (2003).

    CAS  PubMed  Article  Google Scholar 

  18. Kobor, M. S. et al. A protein complex containing the conserved Swi2/Snf2-related ATPase Swr1p deposits histone variant H2A. Z into euchromatin. PLoS Biol. 2, E131 (2004). References 14, 17 and 18 report the identification of SWR1 as the remodeller ATPase that places the histone H2A variant Htz1 into chromatin.

    PubMed  PubMed Central  Article  Google Scholar 

  19. Zhang, H., Roberts, D. N. & Cairns, B. R. Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss. Cell 123, 219?231 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. Vignali, M., Hassan, A. H., Neely, K. E. & Workman, J. L. ATP-dependent chromatin-remodeling complexes. Mol. Cell. Biol. 20, 1899?1910 (2000).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. Cairns, B. R. et al. RSC, an essential, abundant chromatin-remodeling complex. Cell 87, 1249?1260 (1996).

    CAS  Article  PubMed  Google Scholar 

  22. Ito, T., Bulger, M., Pazin, M. J., Kobayashi, R. & Kadonaga, J. T. ACF, an ISWI-containing and ATP-utilizing chromatin assembly and remodeling factor. Cell 90, 145?155 (1997).

    CAS  PubMed  Article  Google Scholar 

  23. Laurent, B. C., Yang, X. & Carlson, M. An essential Saccharomyces cerevisiae gene homologous to SNF2 encodes a helicase-related protein in a new family. Mol. Cell. Biol. 12, 1893?1902 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Eisen, J. A., Sweder, K. S. & Hanawalt, P. C. Evolution of the SNF2 family of proteins: subfamilies with distinct sequences and functions. Nucleic Acids Res. 23, 2715?2723 (1995).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. Winston, F. & Allis, C. D. The bromodomain: a chromatin-targeting module? Nature Struct. Biol. 6, 601?604 (1999).

    CAS  Article  PubMed  Google Scholar 

  26. Hassan, A. H. et al. Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes. Cell 111, 369?379 (2002).

    CAS  PubMed  Article  Google Scholar 

  27. Kasten, M. et al. Tandem bromodomains in the chromatin remodeler RSC recognize acetylated histone H3 Lys14. EMBO J. 23, 1348?1359 (2004).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    PubMed  Article  Google Scholar 

  29. Haushalter, K. A. & Kadonaga, J. T. Chromatin assembly by DNA-translocating motors. Nature Rev. Mol. Cell Biol. 4, 613?620 (2003).

    CAS  Article  Google Scholar 

  30. Corona, D. F. & Tamkun, J. W. Multiple roles for ISWI in transcription, chromosome organization and DNA replication. Biochim. Biophys. Acta 1677, 113?119 (2004).

    CAS  PubMed  Article  Google Scholar 

  31. Deuring, R. et al. The ISWI chromatin-remodeling protein is required for gene expression and the maintenance of higher order chromatin structure in vivo. Mol. Cell 5, 355?365 (2000).

    CAS  PubMed  Article  Google Scholar 

  32. Goldmark, J. P., Fazzio, T. G., Estep, P. W., Church, G. M. & Tsukiyama, T. The Isw2 chromatin remodeling complex represses early meiotic genes upon recruitment by Ume6p. Cell 103, 423?433 (2000).

    CAS  PubMed  Article  Google Scholar 

  33. Martens, J. A. & Winston, F. Recent advances in understanding chromatin remodeling by Swi/Snf complexes. Curr. Opin. Genet. Dev. 13, 136?142 (2003).

    CAS  PubMed  Article  Google Scholar 

  34. Morillon, A. et al. Isw1 chromatin remodeling ATPase coordinates transcription elongation and termination by RNA polymerase II. Cell 115, 425?435 (2003).

    CAS  PubMed  Article  Google Scholar 

  35. Martens, J. A. & Winston, F. Evidence that Swi/Snf directly represses transcription in S. cerevisiae. Genes Dev. 16, 2231?2236 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  36. Varga-Weisz, P. D. et al. Chromatin-remodelling factor CHRAC contains the ATPases ISWI and topoisomerase II. Nature 388, 598?602 (1997).

    CAS  PubMed  Article  Google Scholar 

  37. Flaus, A. & Owen-Hughes, T. Dynamic properties of nucleosomes during thermal and ATP-driven mobilization. Mol. Cell. Biol. 23, 7767?7779 (2003).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. Owen-Hughes, T., Utley, R. T., Cote, J., Peterson, C. L. & Workman, J. L. Persistent site-specific remodeling of a nucleosome array by transient action of the SWI/SNF complex. Science 273, 513?516 (1996).

    CAS  PubMed  Article  Google Scholar 

  39. Kal, A. J., Mahmoudi, T., Zak, N. B. & Verrijzer, C. P. The Drosophila Brahma complex is an essential coactivator for the trithorax group protein Zeste. Genes Dev. 14, 1058?1071 (2000).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. Whitehouse, I. et al. Nucleosome mobilization catalysed by the yeast SWI/SNF complex. Nature 400, 784?787 (1999).

    CAS  PubMed  Article  Google Scholar 

  41. Kassabov, S. R., Zhang, B., Persinger, J. & Bartholomew, B. SWI/SNF unwraps, slides, and rewraps the nucleosome. Mol. Cell 11, 391?403 (2003). References 37 and 41 show that nucleosome repositioning by SWI/SNF remodellers enables DNA unwrapping from the edge of the nucleosome, disrupting up to 4?5 histone?DNA contacts.

    CAS  PubMed  Article  Google Scholar 

  42. Langst, G., Bonte, E. J., Corona, D. F. & Becker, P. B. Nucleosome movement by CHRAC and ISWI without disruption or trans-displacement of the histone octamer. Cell 97, 843?852 (1999). References 40 and 42 provide biochemical evidence for nucleosome sliding along the DNA without complete dissociation/reassociation of the histone octamer.

    CAS  PubMed  Article  Google Scholar 

  43. Phelan, M. L., Sif, S., Narlikar, G. J. & Kingston, R. E. Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits. Mol. Cell 3, 247?253 (1999).

    CAS  PubMed  Article  Google Scholar 

  44. Corona, D. F. et al. ISWI is an ATP-dependent nucleosome remodeling factor. Mol. Cell 3, 239?245 (1999). References 43 and 44 demonstrate that the ATPase subunit in isolation can achieve limited remodelling in vitro.

    CAS  PubMed  Article  Google Scholar 

  45. Singleton, M. R. & Wigley, D. B. Modularity and specialization in superfamily 1 and 2 helicases. J. Bacteriol. 184, 1819?1826 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. Murray, N. E. Type I restriction systems: sophisticated molecular machines. Microbiol. Mol. Biol. Rev. 64, 412?434 (2000).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. Kim, J. L. et al. Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding. Structure 6, 89?100 (1998).

    CAS  PubMed  Article  Google Scholar 

  48. Velankar, S. S., Soultanas, P., Dillingham, M. S., Subramanya, H. S. & Wigley, D. B. Crystal structures of complexes of PcrA DNA helicase with a DNA substrate indicate an inchworm mechanism. Cell 97, 75?84. (1999). This study presents two different structures of PcrA, providing snapshots of different steps of ATP-dependent DNA translocation.

    CAS  Article  PubMed  Google Scholar 

  49. Singleton, M. R., Scaife, S. & Wigley, D. B. Structural analysis of DNA replication fork reversal by RecG. Cell 107, 79?89 (2001).

    CAS  PubMed  Article  Google Scholar 

  50. Saha, A., Wittmeyer, J. & Cairns, B. R. Chromatin remodeling through directional DNA translocation from an internal nucleosomal site. Nature Struct. Mol. Biol. 12, 747?755 (2005). This report, along with reference 59, demonstrates that remodellers translocate nucleosomal DNA from a fixed internal site on the nucleosome.

    CAS  Article  Google Scholar 

  51. Lia, G. et al. Direct observation of DNA distortion by the RSC complex. Mol. Cell 21, 417?425 (2006). Reference 51 provides the first evidence for translocation by a remodeller in a single-molecule format.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  52. Lorch, Y., Cairns, B. R., Zhang, M. & Kornberg, R. D. Activated RSC?nucleosome complex and persistently altered form of the nucleosome. Cell 94, 29?34 (1998).

    CAS  PubMed  Article  Google Scholar 

  53. Langst, G. & Becker, P. B. ISWI induces nucleosome sliding on nicked DNA. Mol. Cell 8, 1085?1092 (2001).

    CAS  PubMed  Article  Google Scholar 

  54. Strohner, R. et al. A 'loop recapture' mechanism for ACF-dependent nucleosome remodeling. Nature Struct. Mol. Biol. 12, 683?690 (2005).

    CAS  Article  Google Scholar 

  55. 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).

    CAS  PubMed  Article  Google Scholar 

  56. 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). References 55 and 56 describe how ISWI remodellers engage nucleosome substrates, showing interaction near the dyad and also with proximal linker DNA.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  57. 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).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  58. Corona, D. F., Clapier, C. R., Becker, P. B. & Tamkun, J. W. Modulation of ISWI function by site-specific histone acetylation. EMBO Rep. 3, 242?247 (2002). References 57 and 58 provide evidence for the role of the N-terminal tail of histone H4 in regulating the activity of ISWI remodellers.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  59. Zofall, M., Persinger, J., Kassabov, S. R. & Bartholomew, B. Chromatin remodeling by ISW2 and SWI/SNF requires DNA translocation inside the nucleosome. Nature Struct. Mol. Biol. 13, 339?346 (2006).

    CAS  Article  Google Scholar 

  60. Thoma, N. H. et al. Structure of the SWI2/SNF2 chromatin-remodeling domain of eukaryotic Rad54. Nature Struct. Mol. Biol. 12, 350?356 (2005).

    Article  CAS  Google Scholar 

  61. Dillingham, M. S., Wigley, D. B. & Webb, M. R. Demonstration of unidirectional single-stranded DNA translocation by PcrA helicase: measurement of step size and translocation speed. Biochemistry 39, 205?212 (2000).

    CAS  PubMed  Article  Google Scholar 

  62. Dumont, S. et al. RNA translocation and unwinding mechanism of HCV NS3 helicase and its coordination by ATP. Nature 439, 105?108 (2006). Provides single-molecule evidence for the inchworming mechanism of DNA translocation by SF2 family translocases and the concept of sub-steps by the tracking domain.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  63. Gavin, I., Horn, P. J. & Peterson, C. L. SWI/SNF chromatin remodeling requires changes in DNA topology. Mol. Cell 7, 97?104 (2001).

    CAS  PubMed  Article  Google Scholar 

  64. Havas, K. et al. Generation of superhelical torsion by ATP-dependent chromatin remodeling activities. Cell 103, 1133?1142 (2000). References 63 and 64 demonstrate that remodellers generate torsional stress during remodelling.

    CAS  PubMed  Article  Google Scholar 

  65. 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).

    CAS  PubMed  Article  Google Scholar 

  66. Fitzgerald, D. J. et al. Reaction cycle of the yeast Isw2 chromatin remodeling complex. EMBO J. 23, 3836?3843 (2004).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  67. Lorch, Y., Davis, B. & Kornberg, R. D. Chromatin remodeling by DNA bending, not twisting. Proc. Natl Acad. Sci. USA 102, 1329?1332 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  68. Fyodorov, D. V. & Kadonaga, J. T. Dynamics of ATP-dependent chromatin assembly by ACF. Nature 418, 897?900 (2002).

    CAS  PubMed  Article  Google Scholar 

  69. Rastelli, L. & Kuroda, M. I. An analysis of maleless and histone H4 acetylation in Drosophila melanogaster spermatogenesis. Mech. Dev. 71, 107?117 (1998).

    CAS  PubMed  Article  Google Scholar 

  70. Narlikar, G. J., Phelan, M. L. & Kingston, R. E. Generation and interconversion of multiple distinct nucleosomal states as a mechanism for catalyzing chromatin fluidity. Mol. Cell 8, 1219?1230 (2001).

    CAS  PubMed  Article  Google Scholar 

  71. Suto, R. K. et al. Crystal structures of nucleosome core particles in complex with minor groove DNA-binding ligands. J. Mol. Biol. 326, 371?380 (2003).

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  73. Reinke, H. & Horz, W. Histones are first hyperacetylated and then lose contact with the activated PHO5 promoter. Mol. Cell 11, 1599?1607 (2003).

    CAS  Article  PubMed  Google Scholar 

  74. Boeger, H., Griesenbeck, J., Strattan, J. S. & Kornberg, R. D. Removal of promoter nucleosomes by disassembly rather than sliding in vivo. Mol. Cell 14, 667?673 (2004).

    CAS  PubMed  Article  Google Scholar 

  75. Lee, C. K., Shibata, Y., Rao, B., Strahl, B. D. & Lieb, J. D. Evidence for nucleosome depletion at active regulatory regions genome-wide. Nature Genet. 36, 900?905 (2004).

    CAS  PubMed  Article  Google Scholar 

  76. Lorch, Y., Zhang, M. & Kornberg, R. D. Histone octamer transfer by a chromatin-remodeling complex. Cell 96, 389?392 (1999). References 73?76 provide evidence for nucleosome loss in vivo and in vitro.

    CAS  PubMed  Article  Google Scholar 

  77. Phelan, M. L., Schnitzler, G. R. & Kingston, R. E. Octamer transfer and creation of stably remodeled nucleosomes by human SWI?SNF and its isolated ATPases. Mol. Cell. Biol. 20, 6380?6389 (2000).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  78. Hamiche, A., Sandaltzopoulos, R., Gdula, D. A. & Wu, C. ATP-dependent histone octamer sliding mediated by the chromatin remodeling complex NURF. Cell 97, 833?842 (1999).

    CAS  PubMed  Article  Google Scholar 

  79. Widom, J. Structure, dynamics, and function of chromatin in vitro. Annu. Rev. Biophys. Biomol. Struct. 27, 285?327 (1998).

    CAS  PubMed  Article  Google Scholar 

  80. Li, G. & Widom, J. Nucleosomes facilitate their own invasion. Nature Struct. Mol. Biol. 11, 763?769 (2004).

    CAS  Article  Google Scholar 

  81. Li, G., Levitus, M., Bustamante, C. & Widom, J. Rapid spontaneous accessibility of nucleosomal DNA. Nature Struct. Mol. Biol. 12, 46?53 (2005).

    CAS  Article  Google Scholar 

  82. Widom, J. Role of DNA sequence in nucleosome stability and dynamics. Q. Rev. Biophys. 34, 269?324 (2001).

    CAS  PubMed  Article  Google Scholar 

  83. Gottesfeld, J. M. & Luger, K. Energetics and affinity of the histone octamer for defined DNA sequences. Biochemistry 40, 10927?10933 (2001).

    CAS  PubMed  Article  Google Scholar 

  84. Hirschhorn, J. N., Brown, S. A., Clark, C. D. & Winston, F. Evidence that SNF2/SWI2 and SNF5 activate transcription in yeast by altering chromatin structure. Genes Dev. 6, 2288?2298 (1992).

    CAS  Article  PubMed  Google Scholar 

  85. Sudarsanam, P., Iyer, V. R., Brown, P. O. & Winston, F. Whole-genome expression analysis of snf/swi mutants of Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 97, 3364?3369 (2000).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  86. Davie, J. K. & Kane, C. M. Genetic interactions between TFIIS and the Swi-Snf chromatin-remodeling complex. Mol. Cell. Biol. 20, 5960?5973 (2000).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  87. Chai, B., Huang, J., Cairns, B. R. & Laurent, B. C. Distinct roles for the RSC and Swi/Snf ATP-dependent chromatin remodelers in DNA double-strand break repair. Genes Dev. 19, 1656?1661 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  88. Neely, K. E., Hassan, A. H., Brown, C. E., Howe, L. & Workman, J. L. Transcription activator interactions with multiple SWI/SNF subunits. Mol. Cell. Biol. 22, 1615?1625 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  89. Yudkovsky, N., Logie, C., Hahn, S. & Peterson, C. L. Recruitment of the SWI/SNF chromatin remodeling complex by transcriptional activators. Genes Dev. 13, 2369?2374 (1999).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  90. Ng, H. H., Robert, F., Young, R. A. & Struhl, K. Genome-wide location and regulated recruitment of the RSC nucleosome-remodeling complex. Genes Dev. 16, 806?819 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  91. Angus-Hill, M. L. et al. A Rsc3/Rsc30 zinc cluster dimer reveals novel roles for the chromatin remodeler RSC in gene expression and cell cycle control. Mol. Cell 7, 741?751 (2001).

    CAS  PubMed  Article  Google Scholar 

  92. Moreira, J. M. & Holmberg, S. Transcriptional repression of the yeast CHA1 gene requires the chromatin-remodeling complex RSC. EMBO J. 18, 2836?2844 (1999).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  93. Damelin, M. et al. The genome-wide localization of Rsc9, a component of the RSC chromatin-remodeling complex, changes in response to stress. Mol. Cell 9, 563?573 (2002).

    CAS  PubMed  Article  Google Scholar 

  94. Huang, J. & Laurent, B. C. A Role for the RSC chromatin remodeler in regulating cohesion of sister chromatid arms. Cell Cycle 3, 973?975 (2004).

    CAS  PubMed  Google Scholar 

  95. Wong, M. C., Scott-Drew, S. R., Hayes, M. J., Howard, P. J. & Murray, J. A. RSC2, encoding a component of the RSC nucleosome remodeling complex, is essential for 2μm plasmid maintenance in Saccharomyces cerevisiae. Mol. Cell. Biol. 22, 4218?4229 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  96. Huang, J., Hsu, J. M. & Laurent, B. C. The RSC nucleosome-remodeling complex is required for cohesin's association with chromosome arms. Mol. Cell 13, 739?750 (2004).

    CAS  PubMed  Article  Google Scholar 

  97. Cao, Y., Cairns, B. R., Kornberg, R. D. & Laurent, B. C. Sfh1p, a component of a novel chromatin-remodeling complex, is required for cell cycle progression. Mol. Cell. Biol. 17, 3323?3334 (1997).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  98. Armstrong, J. A. et al. The Drosophila BRM complex facilitates global transcription by RNA polymerase II. EMBO J. 21, 5245?5254 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  99. Zraly, C. B., Marenda, D. R. & Dingwall, A. K. SNR1 (INI1/SNF5) mediates important cell growth functions of the Drosophila Brahma (SWI/SNF) chromatin remodeling complex. Genetics 168, 199?214 (2004).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  100. Marenda, D. R., Zraly, C. B., Feng, Y., Egan, S. & Dingwall, A. K. The Drosophila SNR1 (SNF5/INI1) subunit directs essential developmental functions of the Brahma chromatin remodeling complex. Mol. Cell. Biol. 23, 289?305 (2003).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  101. Srinivasan, S. et al. The Drosophila trithorax group protein Kismet facilitates an early step in transcriptional elongation by RNA polymerase II. Development 132, 1623?1635 (2005).

    CAS  PubMed  Article  Google Scholar 

  102. Roberts, C. W., Galusha, S. A., McMenamin, M. E., Fletcher, C. D. & Orkin, S. H. Haploinsufficiency of Snf5 (integrase interactor 1) predisposes to malignant rhabdoid tumors in mice. Proc. Natl Acad. Sci. USA 97, 13796?13800 (2000).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  103. Wong, A. K. et al. BRG1, a component of the SWI-SNF complex, is mutated in multiple human tumor cell lines. Cancer Res. 60, 6171?6177 (2000).

    CAS  PubMed  Google Scholar 

  104. Hendricks, K. B., Shanahan, F. & Lees, E. Role for BRG1 in cell cycle control and tumor suppression. Mol. Cell. Biol. 24, 362?376 (2004).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  105. Gresh, L. et al. The SWI/SNF chromatin-remodeling complex subunit SNF5 is essential for hepatocyte differentiation. EMBO J. 24, 3313?3324 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  106. Vradii, D. et al. Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes. J. Cell Physiol. 206, 112?118 (2006).

    CAS  PubMed  Article  Google Scholar 

  107. de la Serna, I. L., Carlson, K. A. & Imbalzano, A. N. Mammalian SWI/SNF complexes promote MyoD-mediated muscle differentiation. Nature Genet. 27, 187?190 (2001).

    CAS  PubMed  Article  Google Scholar 

  108. Bultman, S. et al. A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes. Mol. Cell 6, 1287?1295 (2000).

    CAS  PubMed  Article  Google Scholar 

  109. Wang, Z. et al. Polybromo protein BAF180 functions in mammalian cardiac chamber maturation. Genes Dev. 18, 3106?3116 (2004).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  110. Lickert, H. et al. Baf60c is essential for function of BAF chromatin remodelling complexes in heart development. Nature 432, 107?112 (2004).

    CAS  PubMed  Article  Google Scholar 

  111. Corey, L. L., Weirich, C. S., Benjamin, I. J. & Kingston, R. E. Localized recruitment of a chromatin-remodeling activity by an activator in vivo drives transcriptional elongation. Genes Dev. 17, 1392?1401 (2003).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  112. Zhao, K. et al. Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling. Cell 95, 625?636 (1998).

    CAS  Article  PubMed  Google Scholar 

  113. Batsche, E., Yaniv, M. & Muchardt, C. The human SWI/SNF subunit Brm is a regulator of alternative splicing. Nature Struct. Mol. Biol. 13, 22?29 (2006).

    CAS  Article  Google Scholar 

  114. Vary, J. C., Jr. et al. Yeast Isw1p forms two separable complexes in vivo. Mol. Cell. Biol. 23, 80?91 (2003).

    CAS  PubMed  Article  Google Scholar 

  115. Bozhenok, L., Wade, P. A. & Varga-Weisz, P. WSTF?ISWI chromatin remodeling complex targets heterochromatic replication foci. EMBO J. 21, 2231?2241 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  116. Collins, N. et al. An ACF1?ISWI chromatin-remodeling complex is required for DNA replication through heterochromatin. Nature Genet. 32, 627?632 (2002).

    CAS  Article  PubMed  Google Scholar 

  117. Hakimi, M. A. et al. A chromatin remodelling complex that loads cohesin onto human chromosomes. Nature 418, 994?998 (2002).

    CAS  PubMed  Article  Google Scholar 

  118. Stopka, T. & Skoultchi, A. I. The ISWI ATPase Snf2h is required for early mouse development. Proc. Natl Acad. Sci. USA 100, 14097?14102 (2003).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  119. Badenhorst, P., Voas, M., Rebay, I. & Wu, C. Biological functions of the ISWI chromatin remodeling complex NURF. Genes Dev. 16, 3186?3198 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  120. Shen, X., Mizuguchi, G., Hamiche, A. & Wu, C. A chromatin remodelling complex involved in transcription and DNA processing. Nature 406, 541?544 (2000).

    CAS  PubMed  Article  Google Scholar 

  121. van Attikum, H., Fritsch, O., Hohn, B. & Gasser, S. M. Recruitment of the INO80 complex by H2A phosphorylation links ATP-dependent chromatin remodeling with DNA double-strand break repair. Cell 119, 777?788 (2004).

    CAS  PubMed  Article  Google Scholar 

  122. Morrison, A. J. et al. INO80 and γ-H2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair. Cell 119, 767?775 (2004).

    CAS  PubMed  Article  Google Scholar 

  123. Jonsson, Z. O., Jha, S., Wohlschlegel, J. A. & Dutta, A. Rvb1p/Rvb2p recruit Arp5p and assemble a functional Ino80 chromatin remodeling complex. Mol. Cell 16, 465?477 (2004).

    CAS  PubMed  Article  Google Scholar 

  124. Fritsch, O., Benvenuto, G., Bowler, C., Molinier, J. & Hohn, B. The INO80 protein controls homologous recombination in Arabidopsis thaliana. Mol. Cell 16, 479?485 (2004).

    CAS  PubMed  Article  Google Scholar 

  125. Kusch, T. et al. Acetylation by Tip60 Is required for selective histone variant exchange at DNA lesions. Science 306, 2084?2087 (2004).

    CAS  PubMed  Article  Google Scholar 

  126. Wade, P. A. et al. Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation. Nature Genet. 23, 62?66 (1999).

    CAS  PubMed  Article  Google Scholar 

  127. Jones, P. L. et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nature Genet. 19, 187?191 (1998).

    CAS  Article  PubMed  Google Scholar 

  128. Unhavaithaya, Y. et al. MEP-1 and a homolog of the NURD complex component Mi-2 act together to maintain germline?soma distinctions in C. elegans. Cell 111, 991?1002 (2002).

    CAS  PubMed  Article  Google Scholar 

  129. von Zelewsky, T. et al. The C. elegans Mi-2 chromatin-remodelling proteins function in vulval cell fate determination. Development 127, 5277?5284 (2000).

    CAS  PubMed  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bradley R. Cairns.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Bradley Cairns' homepage

Glossary

Kinetochore

A large multi-protein complex that assembles onto the centromere of the mitotic chromosome. It links the chromosome to the microtubules of the mitotic spindle to segregate sister chromatids towards the spindle poles.

Centromere

The region of a mitotic chromosome on which the kinetochore assembles.

Telomere

The end of a normal chromosome, which consists of a repeating sequence that is extended by a telomerase to prevent the shortening of DNA that accompanies replication.

Bromodomain

A motif that is common in chromatin factors and that binds to acetylated lysine residues in histone tails and other proteins.

SANT domain

An evolutionarily conserved protein domain so named because it is commonly found in Swi3, Ada2, N-CoR and TFIIIB. It is important for DNA and histone-tail binding.

SLIDE domain

A SANT-like ISWI domain that interacts with DNA.

Translational position

The precise 146-bp region on which the nucleosome resides in a DNA molecule.

DEAD/H-box ATPase domain

An evolutionarily conserved protein domain that is present in DEAD/H-box proteins with ATP-dependent helicase/translocase activity and that contains seven characteristic motifs.

Helicase

A motor protein that uses the energy of ATP hydrolysis to unwind nucleic-acid duplexes.

Nucleosome dyad

The centre of the nucleosome around which there is an overall pseudo two-fold symmetry.

RecA-like domain

A structurally conserved domain that is found in helicases, which probably evolved from the Escherichia coli RecA protein that couples cycles of nucleotide binding and hydrolysis to nucleic-acid translocation.

One-dimensional diffusion

A random walk with one degree of freedom. In this context, it refers to movement of the torsional strain that is imposed on histone?DNA contacts along the length of DNA in the nucleosome.

B-form of DNA

The native form of the right-handed DNA helix with 10.6 base pairs per helical turn.

Dosage compensation

The process of equalizing the gene dosage of the X chromosome in males with the two X chromosomes in females.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Saha, A., Wittmeyer, J. & Cairns, B. Chromatin remodelling: the industrial revolution of DNA around histones. Nat Rev Mol Cell Biol 7, 437–447 (2006). https://doi.org/10.1038/nrm1945

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm1945

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing