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.

  • Review Article
  • Published:

Chromatin assembly by DNA-translocating motors

Key Points

  • Chromatin assembly in vivo occurs during DNA replication in cycling cells and in a replication-independent fashion throughout the cell cycle.

  • Histone chaperones, such as CAF1, RCAF/ASF1, NAP1 and HIR proteins, bind to histones and participate in their deposition onto DNA.

  • ATP-dependent factors, such as ACF and RSF, use the energy of ATP hydrolysis to assemble periodic arrays of nucleosomes.

  • ACF seems to function as a DNA-translocating enzyme during chromatin assembly.

  • In the iterative-annealing model for chromatin assembly, non-nucleosomal histone–DNA complexes are resolved into nucleosomes through the iterative disruption and re-establishment of histone–DNA contacts by an ATP-driven DNA-translocating enzyme.

  • In the directed-deposition model for chromatin assembly, a DNA-translocating motor functions in conjunction with the histone–chaperone complex to mediate the processive formation of nucleosome arrays.

Abstract

Chromatin assembly is required for the duplication of eukaryotic chromosomes and functions at the interface between cell-cycle progression and gene expression. The central machinery that mediates chromatin assembly consists of histone chaperones, which deliver histones to the DNA, and ATP-utilizing motor proteins, which are DNA-translocating factors that act in conjunction with the histone chaperones to mediate the deposition of histones into periodic nucleosome arrays. Here, we describe these factors and propose possible mechanisms by which DNA-translocating motors might catalyse chromatin assembly.

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

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: A simple view of chromatin assembly.
Figure 2: Iterative-annealing model of chromatin assembly.
Figure 3: Nucleosome mobilization by a DNA-translocating enzyme.
Figure 4: Directed-deposition model of chromatin assembly.

Similar content being viewed by others

References

  1. Verreault, A. De novo nucleosome assembly: new pieces in an old puzzle. Genes Dev. 14, 1430–1438 (2000).

    Article  CAS  PubMed  Google Scholar 

  2. Mello, J. A. & Almouzni, G. The ins and outs of nucleosome assembly. Curr. Opin. Genet. Dev. 11, 136–141 (2001).

    Article  CAS  PubMed  Google Scholar 

  3. Tyler, J. K. Chromatin assembly. Eur. J. Biochem. 269, 2268–2274 (2002).

    Article  CAS  PubMed  Google Scholar 

  4. Krude, T. & Keller, C. Chromatin assembly during S phase: contributions from histone deposition, DNA replication and the cell division cycle. Cell Mol. Life Sci. 58, 665–672 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Kadam, S. & Emerson, B. M. Mechanisms of chromatin assembly and transcription. Curr. Opin. Cell Biol. 14, 262–268 (2002).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Redon, C. et al. Histone H2A variants H2AX and H2AZ. Curr. Opin. Genet. Dev. 12, 162–169 (2002).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bustin, M. Chromatin unfolding and activation by HMGN(*) chromosomal proteins. Trends Biochem. Sci. 26, 431–437 (2001).

    Article  CAS  PubMed  Google Scholar 

  10. Bird, A. P. Functions for DNA methylation in vertebrates. Cold Spring Harb. Symp. Quant. Biol. 58, 281–285 (1993).

    Article  CAS  PubMed  Google Scholar 

  11. Sobel, R. E., Cook, R. G., Perry, C. A., Annunziato, A. T. & Allis, C. D. Conservation of deposition-related acetylation sites in newly synthesized histones H3 and H4. Proc. Natl Acad. Sci. USA 92, 1237–1241 (1995). Reports the identification of conserved sites of acetylation of newly synthesized histones H3 and H4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Shibahara, K. -I., Verreault, A. & Stillman, B. The N-terminal domains of histones H3 and H4 are not necessary for chromatin assembly factor-1-mediated nucleosome assembly onto replicated DNA in vitro. Proc. Natl Acad. Sci. USA 97, 7766–7771 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Levenstein, M. E. & Kadonaga, J. T. Biochemical analysis of chromatin containing recombinant Drosophila core histones. J. Biol. Chem. 277, 8749–8754 (2001).

    Article  PubMed  CAS  Google Scholar 

  14. Ahmad, K. & Henikoff, S. Epigenetic consequences of nucleosome dynamics. Cell 111, 281–284 (2002).

    Article  CAS  PubMed  Google Scholar 

  15. Ahmad, K. & Henikoff, S. The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. Mol. Cell 9, 1191–1200 (2002). Reports the identification of amino-acid residues that specify distinct chromatin assembly pathways for histones H3 and H3.3.

    Article  CAS  PubMed  Google Scholar 

  16. Ray-Gallet, D. et al. HIRA is critical for a nucleosome assembly pathway independent of DNA synthesis. Mol. Cell 9, 1091–1100 (2002). Reports the analysis of nucleosome assembly by HIRA protein.

    Article  CAS  PubMed  Google Scholar 

  17. Bannister, A. J., Schneider, R. & Kouzarides, T. Histone methylation. Dynamic or static? Cell 109, 801–806 (2002).

    Article  CAS  PubMed  Google Scholar 

  18. Philpott, A., Krude, T. & Laskey, R. A. Nuclear chaperones. Semin. Cell Dev. Biol. 11, 7–14 (2000).

    Article  CAS  PubMed  Google Scholar 

  19. Nakagawa, T., Bulger, M., Muramatsu, M. & Ito, T. Multistep chromatin assembly on supercoiled plasmid DNA by nucleosome assembly protein-1 and ATP-utilizing chromatin assembly and remodeling factor. J. Biol. Chem. 276, 27384–27391 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. Pfaffle, P. & Jackson, V. Studies on rates of nucleosome formation with DNA under stress. J. Biol. Chem. 265, 16821–16829 (1990).

    Article  CAS  PubMed  Google Scholar 

  21. Ito, T. et al. ACF consists of two subunits, Acf1 and ISWI, that function cooperatively in the ATP-dependent catalysis of chromatin assembly. Genes Dev. 13, 1529–1539 (1999). Reports the establishment of a purified recombinant chromatin assembly system with ACF, which consists of ACF1 and ISWI subunits, and NAP1.

    Article  CAS  PubMed  PubMed Central  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). Report of the purification and identification of ACF as an ISWI-containing, ATP-utilizing chromatin assembly factor.

    CAS  PubMed  Google Scholar 

  23. Fyodorov, D. V. & Kadonaga, J. T. Dynamics of ATP-dependent chromatin assembly by ACF. Nature 418, 897–900 (2003). Template commitment by ACF during chromatin assembly indicates a DNA-translocating mechanism.

    Google Scholar 

  24. Ridgway, P. & Almouzni, G. CAF-1 and the inheritance of chromatin states: at the crossroads of DNA replication and repair. J. Cell. Sci. 113, 2647–2658 (2000).

    Article  CAS  PubMed  Google Scholar 

  25. Verreault, A., Kaufman, P. D., Kobayashi, R. & Stillman, B. Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4. Cell 87, 95–104 (1996). Report of the purification of the CAF1 complex (CAC) with histone H3 and specifically acetylated histone H4.

    Article  CAS  PubMed  Google Scholar 

  26. Kaufman, P. D., Kobayashi, R., Kessler, N. & Stillman, B. The p150 and p60 subunits of chromatin assembly factor I: a molecular link between newly synthesized histones and DNA replication. Cell 81, 1105–1114 (1995). Cloning of p150 and p60 subunits of human CAF1.

    Article  CAS  PubMed  Google Scholar 

  27. Smith, S. & Stillman, B. Stepwise assembly of chromatin during DNA replication in vitro. EMBO J. 10, 971–980 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Smith, S. & Stillman, B. Purification and characterization of CAF-I, a human cell factor required for chromatin assembly during DNA replication in vitro. Cell 58, 15–25 (1989).

    Article  CAS  PubMed  Google Scholar 

  29. Taddei, A., Roche, D., Sibarita, J. B., Turner, B. M. & Almouzni, G. Duplication and maintenance of heterochromatin domains. J. Cell Biol. 147, 1153–1166 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Krude, T. Chromatin assembly factor 1 (CAF-1) colocalizes with replication foci in HeLa cell nuclei. Exp. Cell Res. 220, 304–311 (1995).

    Article  CAS  PubMed  Google Scholar 

  31. Shibahara, K. & Stillman, B. Replication-dependent marking of DNA by PCNA facilitates CAF-1-coupled inheritance of chromatin. Cell 96, 575–585 (1999). Identification of PCNA as a link between CAF1 and the DNA replication machinery.

    Article  CAS  PubMed  Google Scholar 

  32. Zhang, Z., Shibahara, K. & Stillman, B. PCNA connects DNA replication to epigenetic inheritance in yeast. Nature 408, 221–225 (2000).

    Article  CAS  PubMed  Google Scholar 

  33. Moggs, J. G. et al. A CAF-1–PCNA-mediated chromatin assembly pathway triggered by sensing DNA damage. Mol. Cell. Biol. 20, 1206–1218 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Enomoto, S., McCune-Zierath, P. D., Gerami-Nejad, M., Sanders, M. A. & Berman, J. RLF2, a subunit of yeast chromatin assembly factor-I, is required for telomeric chromatin function in vivo. Genes Dev. 11, 358–370 (1997).

    Article  CAS  PubMed  Google Scholar 

  35. Enomoto, S. & Berman, J. Chromatin assembly factor I contributes to the maintenance, but not the re-establishment, of silencing at the yeast silent mating loci. Genes Dev. 12, 219–232 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Monson, E. K., de Bruin, D. & Zakian, V. A. The yeast Cac1 protein is required for the stable inheritance of transcriptionally repressed chromatin at telomeres. Proc. Natl Acad. Sci. USA 94, 13081–13086 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kaufman, P. D., Kobayashi, R. & Stillman, B. Ultraviolet radiation sensitivity and reduction of telomeric silencing in Saccharomyces cerevisiae cells lacking chromatin assembly factor-I. Genes Dev. 11, 345–357 (1997).

    Article  CAS  PubMed  Google Scholar 

  38. Kaufman, P. D., Cohen, J. L. & Osley, M. A. Hir proteins are required for position-dependent gene silencing in Saccharomyces cerevisiae in the absence of chromatin assembly factor I. Mol. Cell. Biol. 18, 4793–4806 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Smith, J. S., Caputo, E. & Boeke, J. D. A genetic screen for ribosomal DNA silencing defects identifies multiple DNA replication and chromatin-modulating factors. Mol. Cell. Biol. 19, 3184–3197 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tyler, J. K. et al. The RCAF complex mediates chromatin assembly during DNA replication and repair. Nature 402, 555–560 (1999). Identification and characterization of the RCAF chromatin assembly complex containing Asf1 and specifically acetylated H3 and H4.

    Article  CAS  PubMed  Google Scholar 

  41. Munakata, T., Adachi, N., Yokoyama, N., Kuzuhara, T. & Horikoshi, M. A human homologue of yeast anti-silencing factor has histone chaperone activity. Genes Cells 5, 221–233 (2000).

    Article  CAS  PubMed  Google Scholar 

  42. Emili, A., Schieltz, D. M., Yates, J. R. & Hartwell, L. H. Dynamic interaction of DNA damage checkpoint protein Rad53 with chromatin assembly factor Asf1. Mol. Cell 7, 13–20 (2001).

    Article  CAS  PubMed  Google Scholar 

  43. Le, S., Davis, C., Konopka, J. B. & Sternglanz, R. Two new S-phase-specific genes from Saccharomyces cerevisiae. Yeast 13, 1029–1042 (1997).

    Article  CAS  PubMed  Google Scholar 

  44. Singer, M. S. et al. Identification of high-copy disruptors of telomeric silencing in Saccharomyces cerevisiae. Genetics 150, 613–632 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hu, F., Alcasabas, A. A. & Elledge, S. J. Asf1 links Rad53 to control of chromatin assembly. Genes Dev. 15, 1061–1066 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Qin, S. & Parthun, M. R. Histone H3 and the histone acetyltransferase Hat1p contribute to DNA double-strand break repair. Mol. Cell. Biol. 22, 8353–8365 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Tyler, J. K. et al. Interaction between the Drosophila CAF-1 and ASF1 chromatin assembly factors. Mol. Cell. Biol. 21, 6574–6584 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Mello, J. A. et al. Human Asf1 and CAF-1 interact and synergize in a repair-coupled nucleosome assembly pathway. EMBO Rep. 3, 329–334 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Krawitz, D. C., Kama, T. & Kaufman, P. D. Chromatin assembly factor I mutants defective for PCNA binding require Asf1/Hir proteins for silencing. Mol. Cell. Biol. 22, 614–625 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sharp, J. A., Fouts, E. T., Krawitz, D. C. & Kaufman, P. D. Yeast histone deposition protein Asf1p requires Hir proteins and PCNA for heterochromatic silencing. Curr. Biol. 11, 463–473 (2001). Identification of an interaction between HIR proteins and ASF1 histone chaperone.

    Article  CAS  PubMed  Google Scholar 

  51. Moshkin, Y. M. et al. Histone chaperone ASF1 cooperates with the Brahma chromatin-remodelling machinery. Genes Dev. 16, 2621–2626 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Chimura, T., Kuzuhara, T. & Horikoshi, M. Identification and characterization of CIA/ASF1 as an interactor of bromodomains associated with TFIID. Proc. Natl Acad. Sci. USA 99, 9334–9339 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Osada, S. et al. The yeast SAS (something about silencing) protein complex contains a MYST-type putative acetyltransferase and functions with chromatin assembly factor ASF1. Genes Dev. 15, 3155–3168 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Meijsing, S. H. & Ehrenhofer-Murray, A. E. The silencing complex SAS-I links histone acetylation to the assembly of repressed chromatin by CAF-I and Asf1 in Saccharomyces cerevisiae. Genes Dev. 15, 3169–3182 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Sutton, A., Bucaria, J., Osley, M. A. & Sternglanz, R. Yeast ASF1 protein is required for cell cycle regulation of histone gene transcription. Genetics 158, 587–596 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Xu, H., Kim, U. J., Schuster, T. & Grunstein, M. Identification of a new set of cell cycle-regulatory genes that regulate S-phase transcription of histone genes in Saccharomyces cerevisiae. Mol. Cell. Biol. 12, 5249–5259 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Sherwood, P. W., Tsang, S. V. & Osley, M. A. Characterization of HIR1 and HIR2, two genes required for regulation of histone gene transcription in Saccharomyces cerevisiae. Mol. Cell. Biol. 13, 28–38 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Spector, M. S., Raff, A., DeSilva, H., Lee, K. & Osley, M. A. Hir1p and Hir2p function as transcriptional corepressors to regulate histone gene transcription in the Saccharomyces cerevisiae cell cycle. Mol. Cell. Biol. 17, 545–552 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Lorain, S. et al. Core histones and HIRIP3, a novel histone-binding protein, directly interact with WD repeat protein HIRA. Mol. Cell. Biol. 18, 5546–5556 (1998). Reports the role of HIR proteins in chromatin assembly.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Ishimi, Y. et al. Purification and initial characterization of a protein which facilitates assembly of nucleosome-like structure from mammalian cells. Eur. J. Biochem. 142, 431–439 (1984).

    Article  CAS  PubMed  Google Scholar 

  61. Ishimi, Y., Yasuda, H., Hirosumi, J., Hanaoka, F. & Yamada, M. A protein which facilitates assembly of nucleosome-like structures in vitro in mammalian cells. J. Biochem. 94, 735–744 (1983).

    Article  CAS  PubMed  Google Scholar 

  62. Ito, T., Bulger, M., Kobayashi, R. & Kadonaga, J. T. Drosophila NAP-1 is a core histone chaperone that functions in ATP-facilitated assembly of regularly spaced nucleosomal arrays. Mol. Cell. Biol. 16, 3112–3124 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ishimi, Y. & Kikuchi, A. Identification and molecular cloning of yeast homolog of nucleosome assembly protein I which facilitates nucleosome assembly in vitro. J. Biol. Chem. 266, 7025–7029 (1991).

    Article  CAS  PubMed  Google Scholar 

  64. Ishimi, Y., Kojima, M., Yamada, M. & Hanaoka, F. Binding mode of nucleosome-assembly protein (AP-I) and histones. Eur. J. Biochem. 162, 19–24 (1987).

    Article  CAS  PubMed  Google Scholar 

  65. Chang, L. et al. Histones in transit: cytosolic histone complexes and diacetylation of H4 during nucleosome assembly in human cells. Biochemistry 36, 469–480 (1997).

    Article  CAS  PubMed  Google Scholar 

  66. Rodriguez, P., Pelletier, J., Price, G. B. & Zannis-Hadjopoulos, M. NAP-2: histone chaperone function and phosphorylation state through the cell cycle. J. Mol. Biol. 298, 225–238 (2000).

    Article  CAS  PubMed  Google Scholar 

  67. Mosammaparast, N. et al. Nuclear import of histone H2A and H2B is mediated by a network of karyopherins. J. Cell Biol. 153, 251–262 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Mosammaparast, N., Ewart, C. S. & Pemberton, L. F. A role for nucleosome assembly protein 1 in the nuclear transport of histones H2A and H2B. EMBO J. 21, 6527–6538 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Sharp, J. A., Franco, A. A., Osley, M. A. & Kaufman, P. D. Chromatin assembly factor I and Hir proteins contribute to building functional kinetochores in S. cerevisiae. Genes Dev. 16, 85–100 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Bortvin, A. & Winston, F. Evidence that Spt6p controls chromatin structure by a direct interaction with histones. Science 272, 1473–1476 (1996).

    Article  CAS  PubMed  Google Scholar 

  71. Crevel, G. & Cotterill, S. DF 31, a sperm decondensation factor from Drosophila melanogaster: purification and characterization. EMBO J. 14, 1711–1717 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Crevel, G., Huikeshoven, H. & Cotterill, S. Df31 is a novel nuclear protein involved in chromatin structure in Drosophila melanogaster. J. Cell Sci. 114, 37–47 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Okuwaki, M., Matsumoto, K., Tsujimoto, M. & Nagata, K. Function of nucleophosmin/B23, a nucleolar acidic protein, as a histone chaperone. FEBS Lett. 506, 272–276 (2001).

    Article  CAS  PubMed  Google Scholar 

  74. Okuwaki, M., Tsujimoto, M. & Nagata, K. The RNA binding activity of a ribosome biogenesis factor, nucleophosmin/B23, is modulated by phosphorylation with a cell cycle-dependent kinase and by association with its subtype. Mol. Biol. Cell 13, 2016–2030 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Glikin, G. C., Ruberti, I. & Worcel, A. Chromatin assembly in Xenopus oocytes: in vitro studies. Cell 37, 33–41 (1984). First description of ATP-dependent assembly of periodic nucleosome arrays in vitro with a Xenopus extract.

    Article  CAS  PubMed  Google Scholar 

  76. Alexiadis, V. & Kadonaga, J. T. Strand pairing by Rad54 and Rad51 is enhanced by chromatin. Genes Dev. 16, 2767–2771 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. 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  PubMed  PubMed Central  Google Scholar 

  78. Guschin, D. et al. Multiple ISWI ATPase complexes from Xenopus laevis. Functional conservation of an ACF/CHRAC homolog. J. Biol. Chem. 275, 35248–35255 (2000).

    Article  CAS  PubMed  Google Scholar 

  79. Poot, R. A. et al. HuCHRAC, a human ISWI chromatin remodelling complex contains hACF1 and two novel histone-fold proteins. EMBO J. 19, 3377–3387 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. LeRoy, G., Loyola, A., Lane, W. S. & Reinberg, D. Purification and characterization of a human factor that assembles and remodels chromatin. J. Biol. Chem. 275, 14787–14790 (2000).

    Article  CAS  PubMed  Google Scholar 

  81. LeRoy, G., Orphanides, G., Lane, W. S. & Reinberg, D. Requirement of RSF and FACT for transcription of chromatin templates in vitro. Science 282, 1900–1904 (1998).

    Article  CAS  PubMed  Google Scholar 

  82. Strohner, R. et al. NoRC — a novel member of mammalian ISWI-containing chromatin remodeling machines. EMBO J. 20, 4892–4900 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Bochar, D. A. et al. A family of chromatin remodeling factors related to Williams syndrome transcription factor. Proc. Natl Acad. Sci. USA 97, 1038–1043 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. 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).

    Article  CAS  PubMed  Google Scholar 

  85. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Pazin, M. J. & Kadonaga, J. T. SWI2/SNF2 and related proteins: ATP-driven motors that disrupt protein-DNA interactions? Cell 88, 737–740 (1997).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Tsukiyama, T. The in vivo functions of ATP-dependent chromatin-remodelling factors. Nature Rev. Mol. Cell Biol. 3, 422–429 (2002).

    Article  CAS  Google Scholar 

  89. Narlikar, G. J., Fan, H. Y. & Kingston, R. E. Cooperation between complexes that regulate chromatin structure and transcription. Cell 108, 475–487 (2002).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  91. Flaus, A. & Owen-Hughes, T. Mechanisms for ATP-dependent chromatin remodelling. Curr. Opin. Genet. Dev. 11, 148–154 (2001).

    Article  CAS  PubMed  Google Scholar 

  92. Varga-Weisz, P. D. et al. Chromatin-remodelling factor CHRAC contains the ATPases ISWI and topoisomerase II. Nature 388, 598–602 (1997). Reports the identification of the CHRAC chromatin-remodelling factor, which contains an ISWI subunit.

    Article  CAS  PubMed  Google Scholar 

  93. Eberharter, A. et al. Acf1, the largest subunit of CHRAC, regulates ISWI-induced nucleosome remodelling. EMBO J. 20, 3781–3788 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Corona, D. F. et al. Two histone fold proteins, CHRAC-14 and CHRAC-16, are developmentally regulated subunits of chromatin accessibility complex (CHRAC). EMBO J. 19, 3049–3059 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Tsukiyama, T. & Wu, C. Purification and properties of an ATP-dependent nucleosome remodeling factor. Cell 83, 1011–1020 (1995).

    Article  CAS  PubMed  Google Scholar 

  96. Tsukiyama, T., Daniel, C., Tamkun, J. & Wu, C. ISWI, a member of the SWI2/SNF2 ATPase family, encodes the 140 kDa subunit of the nucleosome remodeling factor. Cell 83, 1021–1026 (1995). The NURF chromatin remodelling factor contains ISWI as a subunit.

    Article  CAS  PubMed  Google Scholar 

  97. Hochheimer, A., Zhou, S., Zheng, S., Holmes, M. C. & Tjian, R. TRF2 associates with DREF and directs promoter-selective gene expression in Drosophila. Nature 420, 439–445 (2002).

    Article  CAS  PubMed  Google Scholar 

  98. Fyodorov, D. V. & Kadonaga, J. T. Binding of Acf1 to DNA involves a WAC motif and is important for ACF-mediated chromatin assembly. Mol. Cell Biol. 22, 6344–6353 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Collins, N. et al. An ACF1-ISWI chromatin-remodeling complex is required for DNA replication through heterochromatin. Nature Genet. 32, 627–632 (2002). RNAi analysis of human ACF1 reveals an effect on DNA replication.

    Article  CAS  PubMed  Google Scholar 

  100. Loyola, A., LeRoy, G., Wang, Y. H. & Reinberg, D. Reconstitution of recombinant chromatin establishes a requirement for histone-tail modifications during chromatin assembly and transcription. Genes Dev. 15, 2837–2851 (2001). ATP-dependent assembly of nucleosome arrays by RSF.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Whitehouse, I., Stockdale, C., Flaus, A., Szczelkun, M. D. & Owen-Hughes, T. Evidence for DNA translocation by the ISWI chromatin remodelling enzyme. Mol. Cell Biol. 23, 1935–1945 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Worcel, A., Han, S. & Wong, M. L. Assembly of newly replicated chromatin. Cell 15, 969–977 (1978). Evidence that histones H3 and H4 deposit onto DNA prior to histones H2A and H2B.

    Article  CAS  PubMed  Google Scholar 

  104. Jackson, V. Deposition of newly synthesized histones: new histones H2A and H2B do not deposit in the same nucleosome with new histones H3 and H4. Biochemistry 26, 2315–2325 (1987).

    Article  CAS  PubMed  Google Scholar 

  105. Thirumalai, D. & Lorimer, G. H. Chaperonin-mediated protein folding. Annu. Rev. Biophys. Biomol. Struct. 30, 245–269 (2001).

    Article  CAS  PubMed  Google Scholar 

  106. Becker, P. B. Nucleosome sliding: facts and fiction. EMBO J. 21, 4749–4753 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Thoma, F., Koller, T. & Klug, A. Involvement of histone H1 in the organization of the nucleosome and of the salt-dependent superstructures of chromatin. J. Cell Biol. 83, 403–427 (1979).

    Article  CAS  PubMed  Google Scholar 

  108. 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).

    Article  CAS  PubMed  Google Scholar 

  109. Grigoryev, S. A. Higher-order folding of heterochromatin: protein bridges span the nucleosome arrays. Biochem. Cell Biol. 79, 227–241 (2001).

    Article  CAS  PubMed  Google Scholar 

  110. Horn, P. J. & Peterson, C. L. Molecular biology: chromatin higher order folding-wrapping up transcription. Science 297, 1824–1827 (2002).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank D. Fyodorov, D. Smith and G. Gemmen for insightful discussions. We further thank D. Fyodorov, B. Santoso, J.-Y. Hsu, T. Juven-Gershon, T. Boulay and V. Alexiadis for critical reading of the manuscript. We apologize to our colleagues whose work could not be cited due to space limitations. K.A.H. is a Robert Black Fellow of the Damon Runyon Cancer Research Foundation. This work was supported by grants from the National Institutes of Health and the VolkswagenStiftung (to J.T.K.)

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to James T. Kadonaga.

Related links

Related links

DATABASES

Flybase

Brahma

CHRAC14

CHRAC16

DF31

NAP1

ISWI

Saccharomyces Genome Database

Asf1

Hir1

Hir2

Kap114

Spt6

Swiss-Prot

ACF1

CAF1

HP1

N1/N2

NAP2

nucleophosmin/B23

nucleoplasmin

RAD53

hSNF2H

TFIID

Glossary

HIGH MOBILITY GROUP PROTEINS

(HMG proteins). Abundant, non-histone chromosomal proteins. There are three families of HMG proteins: HMGB (HMG1/2), HMGN (HMG14/17) and HMGA (HMG-I/-Y).

HETEROCHROMATIN

Chromatin that remains in a condensed state throughout the cell cycle; for example, centromeres and telomeres are heterochromatic regions. Few protein-coding genes are located in heterochromatin and most protein-coding genes are located in euchromatin, which decondenses during interphase.

PCNA

(Proliferating cell nuclear antigen). PCNA is a sliding-clamp protein that forms a doughnut-shaped structure around the DNA, and functions to increase the processivity of DNA polymerases.

KARYOPHERIN

Nuclear import receptor, also known as importin.

CHRAC

(Chromatin accessibility complex). CHRAC was originally identified as a factor that increases the accessibility of restriction enzymes to DNA that is packaged into chromatin.

NURF

(Nucleosome-remodelling factor). NURF was isolated on the basis of its ability to modify the chromatin structure at the hsp70 promoter in cooperation with transcription factors.

TRF2

(TATA-box-binding protein (TBP)-related factor 2). TRF2-containing complexes are involved in transcriptional regulation.

TOPOISOMERASE II

An abundant, ATP-dependent topoisomerase that functions by creating a double-stranded break in the DNA, passing another DNA molecule through this break, and then resealing the double-stranded break. The strand passage reaction relaxes supercoiled substrates and requires ATP.

NUCLEOSOME SLIDING

The translational movement of nucleosomal histones relative to the DNA. Because of the asymmetry of the histone–DNA contacts in the nucleosome, it is unlikely that the histones actually 'slide' along the DNA.

WAC MOTIF

A protein sequence motif that was initially found in WSTF (Williams syndrome transcription factor), ACF1 and cbp147. The WAC motif in ACF1 was found to be required for binding of ACF to DNA.

WAKZ MOTIF

A protein sequence motif that was initially found in WSTF (Williams syndrome transcription factor), ACF1, KIAA0314 and ZK783.4.

DDT DOMAIN

A protein sequence motif found in transcription and chromatin-modifying factors. The sub-region of ACF1 that interacts with ISWI contains a DDT domain.

PHD FINGER

A protein sequence motif that was termed plant homeodomain finger. The PHD finger is found in many proteins that function with chromatin.

BROMODOMAIN

A protein sequence motif that is present in many chromatin-modifying proteins. Bromodomains have been found to bind to acetylated lysine residues.

TRIPLEX DNA DISPLACEMENT ASSAY

A test for DNA translocation in which a short oligonucleotide that binds in the major groove of a pyrimidine-rich target sequence is displaced by motor proteins that translocate through the sequence.

CHAPERONIN

ATP-dependent protein complex that mediates protein folding.

NUCLEOSOME MOBILITY

The ability of nucleosomal histones to move along the DNA. Under physiological conditions, nucleosomes are essentially immobile, but some chromatin-remodelling factors are able to catalyse the movement of nucleosomes.

NUCLEOSOME REMODELLING

Also known as chromatin remodelling. Any detectable change in histone–DNA interactions in a nucleosome. Chromatin-remodelling factors alter the structure of nucleosomes in an ATP-dependent manner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Haushalter, K., Kadonaga, J. Chromatin assembly by DNA-translocating motors. Nat Rev Mol Cell Biol 4, 613–620 (2003). https://doi.org/10.1038/nrm1177

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm1177

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