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.

  • Article
  • Published:

Distinct activities of CHD1 and ACF in ATP-dependent chromatin assembly

Abstract

CHD1 is a chromodomain-containing protein in the SNF2-like family of ATPases. Here we show that CHD1 exists predominantly as a monomer and functions as an ATP-utilizing chromatin assembly factor. This reaction involves purified CHD1, NAP1 chaperone, core histones and relaxed DNA. CHD1 catalyzes the ATP-dependent transfer of histones from the NAP1 chaperone to the DNA by a processive mechanism that yields regularly spaced nucleosomes. The comparative analysis of CHD1 and ACF revealed that CHD1 assembles chromatin with a shorter nucleosome repeat length than ACF. In addition, ACF, but not CHD1, can assemble chromatin containing histone H1, which is involved in the formation of higher-order chromatin structure and transcriptional repression. These results suggest a role for CHD1 in the assembly of active chromatin and a function of ACF in the assembly of repressive chromatin.

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: Drosophila melanogaster CHD1 protein seems to exist predominantly as a monomer.
Figure 2: CHD1 catalyzes the ATP-dependent formation of periodic nucleosome arrays.
Figure 3: Two models for the ATP-dependent formation of periodic nucleosome arrays.
Figure 4: CHD1 and ACF catalyze the periodic spacing of randomly deposited nucleosomes as well as the ATP-dependent transfer of histones from a chaperone protein to DNA.
Figure 5: CHD1 catalyzes the assembly of chromatin by a processive mechanism.
Figure 6: CHD1 and ACF mediate the assembly of chromatin with different nucleosome repeat lengths.
Figure 7: ACF, but not CHD1, can catalyze the assembly of histone H1–containing chromatin.

Similar content being viewed by others

References

  1. Tyler, J.K. Chromatin assembly. Cooperation between histone chaperones and ATP-dependent nucleosome remodeling machines. Eur. J. Biochem. 269, 2268–2274 (2002).

    CAS  PubMed  Google Scholar 

  2. Akey, C.W. & Luger, K. Histone chaperones and nucleosome assembly. Curr. Opin. Struct. Biol. 13, 6–14 (2003).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  4. Loyola, A. & Almouzni, G. Histone chaperones, a supporting role in the limelight. Biochim. Biophys. Acta 1677, 3–11 (2004).

    CAS  PubMed  Google Scholar 

  5. Ito, T., Bulger, M., Kobayashi, R. & Kadonaga, J.T. Drosophila NAP1 is a core histone chaperone that functions in ATP- facilitated assembly of regularly spaced nucleosomal arrays. Mol. Cell. Biol. 16, 3112–3124 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 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).

    CAS  PubMed  Google Scholar 

  7. Tyler, J.K. et al. The RCAF complex mediates chromatin assembly during DNA replication and repair. Nature 402, 555–560 (1999).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  9. 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  Google Scholar 

  10. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Loyola, A. et al. Functional analysis of the subunits of the chromatin assembly factor RSF. Mol. Cell. Biol. 23, 6759–6768 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Kukimoto, I., Elderkin, S., Grimaldi, M., Oelgeschlager, T. & Varga-Weisz, P.D. The histone-fold protein complex CHRAC-15/17 enhances nucleosome sliding and assembly mediated by ACF. Mol. Cell 13, 265–277 (2004).

    CAS  PubMed  Google Scholar 

  14. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Corona, D.F. et al. ISWI is an ATP-dependent nucleosome remodeling factor. Mol. Cell 3, 239–245 (1999).

    CAS  PubMed  Google Scholar 

  16. 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  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  18. 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).

    CAS  PubMed  Google Scholar 

  19. 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  Google Scholar 

  20. Fyodorov, D.V., Blower, M.D., Karpen, G.H. & Kadonaga, J.T. Acf1 confers unique activities to ACF/CHRAC and promotes the formation rather than disruption of chromatin in vivo. Genes Dev. 18, 170–183 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Delmas, V., Stokes, D.G. & Perry, R.P. A mammalian DNA-binding protein that contains a chromodomain and an SNF2/SWI2-like helicase domain. Proc. Natl. Acad. Sci. USA 90, 2414–2418 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Woodage, T., Basrai, M.A., Baxevanis, A.D., Hieter, P. & Collins, F.S. Characterization of the CHD family of proteins. Proc. Natl. Acad. Sci. USA. 94, 11472–11477 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Belotserkovskaya, R. & Reinberg, D. Facts about FACT and transcript elongation through chromatin. Curr. Opin. Genet. Dev. 14, 139–146 (2004).

    CAS  PubMed  Google Scholar 

  24. Stokes, D.G. & Perry, R.P. DNA-binding and chromatin localization properties of CHD1. Mol. Cell. Biol. 15, 2745–2753 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Stokes, D.G., Tartof, K.D. & Perry, R.P. CHD1 is concentrated in interbands and puffed regions of Drosophila polytene chromosomes. Proc. Natl. Acad. Sci. USA. 93, 7137–7142 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Alen, C. et al. A role for chromatin remodeling in transcriptional termination by RNA polymerase II. Mol. Cell 10, 1441–1452 (2002).

    CAS  PubMed  Google Scholar 

  27. Kelley, D.E., Stokes, D.G. & Perry, R.P. CHD1 interacts with SSRP1 and depends on both its chromodomain and its ATPase/helicase-like domain for proper association with chromatin. Chromosoma 108, 10–25 (1999).

    CAS  PubMed  Google Scholar 

  28. Krogan, N.J. et al. RNA polymerase II elongation factors of Saccharomyces cerevisiae: a targeted proteomics approach. Mol. Cell. Biol. 22, 6979–6992 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Simic, R. et al. Chromatin remodeling protein Chd1 interacts with transcription elongation factors and localizes to transcribed genes. EMBO J. 22, 1846–1856 (2003).

    CAS  PubMed  PubMed Central  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).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Robinson, K.M. & Schultz, M.C. Replication-independent assembly of nucleosome arrays in a novel yeast chromatin reconstitution system involves antisilencing factor Asf1p and chromodomain protein Chd1p. Mol. Cell. Biol. 23, 7937–7946 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Tran, H.G., Steger, D.J., Iyer, V.R. & Johnson, A.D. The chromo domain protein chd1p from budding yeast is an ATP-dependent chromatin-modifying factor. EMBO J. 19, 2323–2331 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  34. Lusser, A. & Kadonaga, J.T. Chromatin remodeling by ATP-dependent molecular machines. Bioessays 25, 1192–1200 (2003).

    CAS  PubMed  Google Scholar 

  35. Lusser, A. & Kadonaga, J.T. Strategies for the reconstitution of chromatin. Nat. Methods 1, 19–26 (2004).

    CAS  PubMed  Google Scholar 

  36. Gelbart, M.E., Rechsteiner, T., Richmond, T.J. & Tsukiyama, T. Interactions of Isw2 chromatin remodeling complex with nucleosomal arrays: analyses using recombinant yeast histones and immobilized templates. Mol. Cell. Biol. 21, 2098–2106 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  39. Bates, D.L. & Thomas, J.O. Histones H1 and H5: one or two molecules per nucleosome? Nucleic Acids Res. 9, 5883–5894 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Parseghian, M.H. & Hamkalo, B.A. A compendium of the histone H1 family of somatic subtypes: an elusive cast of characters and their characteristics. Biochem. Cell Biol. 79, 289–304 (2001).

    CAS  PubMed  Google Scholar 

  41. Fyodorov, D.V. & Kadonaga, J.T. Chromatin assembly in vitro with purified recombinant ACF and NAP1. Methods Enzymol. 371, 499–515 (2003).

    CAS  PubMed  Google Scholar 

  42. Stein, A. & Bina, M. A model chromatin assembly system. Factors affecting nucleosome spacing. J. Mol. Biol. 178, 341–363 (1984).

    CAS  PubMed  Google Scholar 

  43. Rodriguez-Campos, A., Shimamura, A. & Worcel, A. Assembly and properties of chromatin containing histone H1. J. Mol. Biol. 209, 135–150 (1989).

    CAS  PubMed  Google Scholar 

  44. Becker, P.B. & Wu, C. Cell-free system for assembly of transcriptionally repressed chromatin from Drosophila embryos. Mol. Cell. Biol. 12, 2241–2249 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Varshavsky, A.J., Bakayev, V.V., & Georgiev, G.P. Heterogeneity of chromatin subunits in vitro and location of histone H1. Nucleic Acids Res. 3, 477–492 (1976).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Laybourn, P.J., & Kadonaga, J.T. Role of nucleosomal cores and histone H1 in regulation of transcription by RNA polymerase II. Science 254, 238–245 (1991).

    CAS  PubMed  Google Scholar 

  47. Thomas, J.O. & Thompson, R.J. Variation in chromatin structure in two cell types from the same tissue: a short DNA repeat length in cerebral cortex neurons. Cell 10, 633–640 (1977).

    CAS  PubMed  Google Scholar 

  48. Villeponteau, B., Brawley, J. & Martinson, H.G. Nucleosome spacing is compressed in active chromatin domains of chick erythroid cells. Biochemistry 31, 1554–1563 (1992).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  50. Belotserkovskaya, R. et al. FACT facilitates transcription-dependent nucleosome alteration. Science 301, 1090–1093 (2003).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank R. Perry, D. Fyodorov, T. Yusufzai, T. Juven-Gershon, J.-Y. Hsu, B. Rattner, T. Boulay and B. Santoso for critical reading of the manuscript. We are grateful to R. Perry and D. Stokes for generously providing antibodies and cDNAs for D. melanogaster CHD1. We are also grateful to K. Robinson for helpful discussions on S. cerevisiae CHD1 as well as to R. Dutnall for the gift of the dNAP1 expression plasmid. A.L. is the recipient of a fellowship from the Austrian Programme for Advanced Research and Technology (APART) of the Austrian Academy of Sciences. This work was supported by grants from the US National Institutes of Health (GM58272) and the VolkswagenStiftung (I/77 995) to J.T.K.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to James T Kadonaga.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lusser, A., Urwin, D. & Kadonaga, J. Distinct activities of CHD1 and ACF in ATP-dependent chromatin assembly. Nat Struct Mol Biol 12, 160–166 (2005). https://doi.org/10.1038/nsmb884

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsmb884

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