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.

The nucleosome surface regulates chromatin compaction and couples it with transcriptional repression

Abstract

Although it is believed that the interconversion between permissive and refractory chromatin structures is important in regulating gene transcription, this process is poorly understood. Central to addressing this issue is to elucidate how a nucleosomal array folds into higher-order chromatin structures. Such findings can then provide new insights into how the folding process is regulated to yield different functional states. Using well-defined in vitro chromatin-assembly and transcription systems, we show that a small acidic region on the surface of the nucleosome is crucial both for the folding of a nucleosomal template into the 30-nm chromatin fiber and for the efficient repression of transcription, thereby providing a mechanistic link between these two essential processes. This structure-function relationship has been exploited by complex eukaryotic cells through the replacement of H2A with the specific variant H2A.Bbd, which naturally lacks an acidic patch.

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: The acidic patch facilitates intranucleosomal interactions.
Figure 2: The partially neutralized acidic patch of H2A.Bbd inhibits the chromatin fiber folding pathway.
Figure 3: The acidic patch inhibits the formation of condensed tertiary chromatin structures.
Figure 4: Efficient transcriptional repression of a chromatin template requires the acidic patch.

References

  1. Tremethick, D.J. Higher-order structures of chromatin: the elusive 30 nm fiber. Cell 128, 651–654 (2007).

    Article  CAS  Google Scholar 

  2. Steger, D.J. & Workman, J.L. Remodeling chromatin structures for transcription: what happens to the histones? Bioessays 18, 875–884 (1996).

    Article  CAS  Google Scholar 

  3. Eberharter, A. & Becker, P.B. Histone acetylation: a switch between repressive and permissive chromatin. Second in review series on chromatin dynamics. EMBO Rep. 3, 224–229 (2002).

    Article  CAS  Google Scholar 

  4. Kornberg, R.D. & Lorch, Y. Chromatin and transcription: where do we go from here. Curr. Opin. Genet. Dev. 12, 249–251 (2002).

    Article  CAS  Google Scholar 

  5. Taylor, I.C., Workman, J.L., Schuetz, T.J. & Kingston, R.E. Facilitated binding of GAL4 and heat shock factor to nucleosomal templates: differential function of DNA-binding domains. Genes Dev. 5, 1285–1298 (1991).

    Article  CAS  Google Scholar 

  6. Tse, C., Sera, T., Wolffe, A.P. & Hansen, J.C. Disruption of higher-order folding by core histone acetylation dramatically enhances transcription of nucleosomal arrays by RNA polymerase III. Mol. Cell. Biol. 18, 4629–4638 (1998).

    Article  CAS  Google Scholar 

  7. Peterson, C.L. & Laniel, M.A. Histones and histone modifications. Curr. Biol. 14, R546–R551 (2004).

    Article  CAS  Google Scholar 

  8. 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  Google Scholar 

  9. Dorigo, B. et al. Nucleosome arrays reveal the two-start organization of the chromatin fiber. Science 306, 1571–1573 (2004).

    Article  CAS  Google Scholar 

  10. Dorigo, B., Schalch, T., Bystricky, K. & Richmond, T.J. Chromatin fiber folding: requirement for the histone H4 N-terminal tail. J. Mol. Biol. 327, 85–96 (2003).

    Article  CAS  Google Scholar 

  11. Fan, J.Y., Rangasamy, D., Luger, K. & Tremethick, D.J. H2A.Z alters the nucleosome surface to promote HP1α-mediated chromatin fiber folding. Mol. Cell 16, 655–661 (2004).

    Article  CAS  Google Scholar 

  12. Shogren-Knaak, M. et al. Histone H4–K16 acetylation controls chromatin structure and protein interactions. Science 311, 844–847 (2006).

    Article  CAS  Google Scholar 

  13. Greaves, I.K., Rangasamy, D., Ridgway, P. & Tremethick, D.J. H2A.Z contributes to the unique 3D structure of the centromere. Proc. Natl. Acad. Sci. USA 104, 525–530 (2007).

    Article  CAS  Google Scholar 

  14. Chadwick, B.P. & Willard, H.F. A novel chromatin protein, distantly related to histone H2A, is largely excluded from the inactive X chromosome. J. Cell Biol. 152, 375–384 (2001).

    Article  CAS  Google Scholar 

  15. Bao, Y. et al. Nucleosomes containing the histone variant H2A.Bbd organize only 118 base pairs of DNA. EMBO J. 23, 3314–3324 (2004).

    Article  CAS  Google Scholar 

  16. Doyen, C.M. et al. Dissection of the unusual structural and functional properties of the variant H2A.Bbd nucleosome. EMBO J. 25, 4234–4244 (2006).

    Article  CAS  Google Scholar 

  17. Fan, J.Y., Gordon, F., Luger, K., Hansen, J.C. & Tremethick, D.J. The essential histone variant H2A.Z regulates the equilibrium between different chromatin conformational states. Nat. Struct. Biol. 9, 172–176 (2002).

    Article  CAS  Google Scholar 

  18. Woodcock, C.L. & Dimitrov, S. Higher-order structure of chromatin and chromosomes. Curr. Opin. Genet. Dev. 11, 130–135 (2001).

    Article  CAS  Google Scholar 

  19. Fletcher, T.M. & Hansen, J.C. The nucleosomal array: structure/function relationships. Crit. Rev. Eukaryot. Gene Expr. 6, 149–188 (1996).

    Article  CAS  Google Scholar 

  20. Horn, P.J., Crowley, K.A., Carruthers, L.M., Hansen, J.C. & Peterson, C.L. The SIN domain of the histone octamer is essential for intramolecular folding of nucleosomal arrays. Nat. Struct. Biol. 9, 167–171 (2002).

    Article  CAS  Google Scholar 

  21. Steger, D.J., Eberharter, A., John, S., Grant, P.A. & Workman, J.L. Purified histone acetyltransferase complexes stimulate HIV-1 transcription from preassembled nucleosomal arrays. Proc. Natl. Acad. Sci. USA 95, 12924–12929 (1998).

    Article  CAS  Google Scholar 

  22. Caravaca, J.M., Cano, S., Gallego, I. & Daban, J.R. Structural elements of bulk chromatin within metaphase chromosomes. Chromosome Res. 13, 725–743 (2005).

    Article  CAS  Google Scholar 

  23. Daban, J.R. & Bermudez, A. Interdigitated solenoid model for compact chromatin fibers. Biochemistry 37, 4299–4304 (1998).

    Article  CAS  Google Scholar 

  24. Horowitz-Scherer, R.A. & Woodcock, C.L. Organization of interphase chromatin. Chromosoma 115, 1–14 (2006).

    Article  Google Scholar 

  25. Greaves, I.K., Rangasamy, D., Devoy, M., Marshall Graves, J.A. & Tremethick, D.J. The X and Y chromosomes assemble into H2A.Z-containing [corrected] facultative heterochromatin [corrected] following meiosis. Mol. Cell. Biol. 26, 5394–5405 (2006).

    Article  CAS  Google Scholar 

  26. Su, A.I. et al. Large-scale analysis of the human and mouse transcriptomes. Proc. Natl. Acad. Sci. USA 99, 4465–4470 (2002).

    Article  CAS  Google Scholar 

  27. Strick, R., Strissel, P.L., Gavrilov, K. & Levi-Setti, R. Cation-chromatin binding as shown by ion microscopy is essential for the structural integrity of chromosomes. J. Cell Biol. 155, 899–910 (2001).

    Article  CAS  Google Scholar 

  28. Belmont, A.S. & Bruce, K. Visualization of G1 chromosomes: a folded, twisted, supercoiled chromonema model of interphase chromatid structure. J. Cell Biol. 127, 287–302 (1994).

    Article  CAS  Google Scholar 

  29. Luger, K., Rechsteiner, T.J. & Richmond, T.J. Preparation of nucleosome core particle from recombinant histones. Methods Enzymol. 304, 3–19 (1999).

    Article  CAS  Google Scholar 

  30. Carruthers, L.M., Tse, C., Walker, K.P., III & Hansen, J.C. Assembly of defined nucleosomal and chromatin arrays from pure components. Methods Enzymol. 304, 19–35 (1999).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We especially thank K. Luger (Colorado State University, Fort Collins) for providing recombinant histones and sharing unpublished data and for many helpful discussions, Y. Bao (Colorado State University, Fort Collins) for recombinant H2A.Bbd, J. Hansen (Colorado State University, Fort Collins) for continued support and critical reading of this manuscript, and T. Soboleva (The John Curtin School of Medical Research) for analysis of published gene expression array data. We also thank D. Rhodes (Medical Research Council Laboratory of Molecular Biology) for the 601-200-12 DNA template and J. Workman (Stowers Institute for Medical Research) for the HIV-208-5S DNA template. This work was supported by an Australian Research grant to J.Y.F. and D.J.T.

Author information

Authors and Affiliations

Authors

Contributions

J.Z. and J.Y.F. carried out the research, D.R. generated mutant histone clones, and D.J.T. devised the project and wrote the paper.

Corresponding author

Correspondence to David J Tremethick.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–4, Supplementary Table 1 (PDF 1063 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zhou, J., Fan, J., Rangasamy, D. et al. The nucleosome surface regulates chromatin compaction and couples it with transcriptional repression. Nat Struct Mol Biol 14, 1070–1076 (2007). https://doi.org/10.1038/nsmb1323

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsmb1323

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