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 history: our view from the bridge

Abstract

Thirty years ago, our conception of chromatin structure underwent a total metamorphosis as the nucleosome era began. In Kurosawa's classic movie 'Rashomon' (1951), each participant had a different perspective of the same pivotal event. This review outlines our perception of history.

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: A fanciful view of chromatin structure.
Figure 2: Superhelical models of chromatin.
Figure 3: A gallery of electron micrographs of chromatin.
Figure 4: A chromatin scientist.

References

  1. Flemming, W. Zellsubstanz, Kern und Zelltheilung (F.C.W. Vogel, Leipzig, 1882).

    Google Scholar 

  2. Paweletz, N. Walther Flemming: pioneer of mitosis research. Nature Rev. Mol. Cell Biol. 2, 72–75 (2001).

    Article  CAS  Google Scholar 

  3. Hughes, A. A History of Cytology 100–101 (Abelard–Schuman, London, 1959).

    Google Scholar 

  4. Bradbury, S. Landmarks in biological light microscopy. J. Microsc. 155, 281–305 (1989).

    Article  Google Scholar 

  5. Bracegirdle, B. The development of biological preparative techniques for light microscopy, 1839–1989. J. Microsc. 155, 307–318 (1989).

    Article  Google Scholar 

  6. Luck, J. M. The Nucleohistones 3–11 (Holden–Day, Inc., San Francisco, 1964).

    Google Scholar 

  7. van Holde, K. E. Chromatin (Springer–Verlag, New York, 1989).

    Book  Google Scholar 

  8. Miescher, F. Ueber die chemische Zusammensetzung der Eiterzellen. Hoppe-Seyler, med. chem. Unters. 4, 441–460 (1871).

    Google Scholar 

  9. Kossel, A. Ueber die chemische Beschaffenheit des Zellkerns. Munchen Med. Wochenschrift. 58, 65–69 (1911).

    CAS  Google Scholar 

  10. Avery, O., MacLeod, C. & McCarty, M. Studies on the chemical nature of the substance inducing transformation of pneumococcal types. J. Exp. Med. 79, 137–158 (1944).

    Article  CAS  Google Scholar 

  11. Felix, K. & Harteneck, A. Ueber den Aufbau des Histons der Thymusdruse. Z. Physiol. Chem. 165, 103–120 (1927).

    Article  CAS  Google Scholar 

  12. Mazia, D. Enzyme studies of chromosomes. Cold Spring Harb. Symp. Quant. Biol. IX, 40–46 (1941).

    Article  Google Scholar 

  13. Schultz, J. The evidence of the nucleoprotein nature of the gene. Cold Spring Harb. Symp. Quant. Biol. IX, 55–65 (1941).

    Article  Google Scholar 

  14. Pauling, L., Corey, R. B. & Branson, H. R. The structure of proteins: two hydrogen-bonded helical configurations of the polypeptide chain. Proc. Natl Acad. Sci. USA 27, 205–211 (1951).

    Article  Google Scholar 

  15. Watson, J. D. & Crick, F. H. C. Molecular structure of nucleic acids. A structure for deoxyribose nucleic acid. Nature 171, 737–738 (1953).

    Article  CAS  Google Scholar 

  16. Wilkins, M. H. F., Stokes, A. R. & Wilson, H. R. Molecular structure of deoxypentose nucleic acids. Nature 171, 738–740 (1953).

    Article  CAS  Google Scholar 

  17. Franklin, R. & Gosling, R. G. Molecular configuration in sodium thymonucleate. Nature 171, 740–741 (1953).

    Article  CAS  Google Scholar 

  18. Gall, J. G. Kinetics of deoxyribonuclease action on chromosomes. Nature 198, 36–38 (1963).

    Article  CAS  Google Scholar 

  19. Johns, E. W. The Histones, Their Interactions with DNA and Some Aspects of Gene Control. 128 (Churchill, London, 1969).

    Google Scholar 

  20. Allfrey, V. G., Faulkner, R. & Mirsky, A. E. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc. Natl Acad. Sci. USA 51, 786–794 (1964).

    Article  CAS  Google Scholar 

  21. Zubay, G. & Doty, P. The isolation and properties of deoxyribonucleoprotein particles. J. Mol. Biol. 1, 1–20 (1959).

    Article  CAS  Google Scholar 

  22. Pardon, J. F., Richards, B. M. & Cotter, R. I. X-ray diffraction studies on oriented nucleohistone gels. Cold Spring Harb. Symp. Quant. Biol. 38, 75–81 (1973).

    Article  Google Scholar 

  23. Everid, A. C., Small, J. V. & Davies, H. G. Electron-microscope observations on the structure of condensed chromatin: evidence for orderly arrays of unit threads on the surface of chicken erythrocyte nuclei. J. Cell Sci. 7, 35–48 (1970).

    CAS  Google Scholar 

  24. Swift, H. The organization of genetic material in eukaryotes: progress and prospects. Cold Spring Harb. Symp. Quant. Biol. 38, 963–979 (1974).

    Article  CAS  Google Scholar 

  25. Olins, D. E. & Olins, A. L. Physical studies of isolated eucaryotic nuclei. J. Cell Biol. 53, 715–736 (1972).

    Article  CAS  Google Scholar 

  26. Clark, R. J. & Felsenfeld, G. Structure of chromatin. Nature New Biol. 229, 101–106 (1971).

    Article  CAS  Google Scholar 

  27. Itzhaki, R. F. Studies on the accessibility of deoxyribonucleic acid in deoxyribonucleoprotein to cationic molecules. Biochem. J. 122, 583–592 (1971).

    Article  CAS  Google Scholar 

  28. Mirsky, A. E. The structure of chromatin. Proc. Natl Acad. Sci. USA 68, 2945–2948 (1971).

    Article  CAS  Google Scholar 

  29. Olins, A. L. & Olins, D. E. Spheroid chromatin units (ν bodies). Science 183, 330–332 (1974).

    Article  CAS  Google Scholar 

  30. Olins, A. L. & Olins, D. E. Spheroid chromatin units (ν bodies). J. Cell Biol. 59, A252 (1973).

    Article  Google Scholar 

  31. Woodcock, C. L. F. Ultrastructure of inactive chromatin. J. Cell Biol. 59, A368 (1973).

    Google Scholar 

  32. Woodcock, C. L., Safer, J. P. & Stanchfield, J. E. Structural repeating units in chromatin. I. Evidence for their general occurrence. Exp. Cell Res. 97, 101–110 (1976).

    Article  CAS  Google Scholar 

  33. D'Anna, J. A. J. & Isenberg, I. A histone cross-complexing pattern. Biochemistry 13, 4992–4997 (1974).

    Article  CAS  Google Scholar 

  34. Roark, D. E., Geoghegan, T. E. & Keller, G. H. A two-subunit histone complex from calf thymus. Biochem. Biophys. Res. Comm. 59, 542–547 (1974).

    Article  CAS  Google Scholar 

  35. Sahasrabuddhe, C. G. & Van Holde, K. E. The effect of trypsin on nuclease-resistant chromatin fragments. J. Biol. Chem. 249, 152–156 (1974).

    CAS  Google Scholar 

  36. Kornberg, R. Chromatin structure: a repeating unit of histones and DNA. Science 184, 868–871 (1974).

    Article  CAS  Google Scholar 

  37. Kornberg, R. D. & Thomas, J. O. Chromatin structure; oligomers of the histones. Science 184, 865–868 (1974).

    Article  CAS  Google Scholar 

  38. Hewish, D. R. & Burgoyne, L. A. Chromatin substructure. The digestion of chromatin at regularly spaced sites by a nuclear deoxyribonuclease. Biochem. Biophys. Res. Comm. 52, 504–510 (1973).

    Article  CAS  Google Scholar 

  39. Oudet, P., Gross-Bellard, M. & Chambon, P. Electron microscopic and biochemical evidence that chromatin structure is a repeating unit. Cell 4, 281–300 (1975).

    Article  CAS  Google Scholar 

  40. Wolffe, A. Chromatin Structure and Function (Academic Press, San Diego, 1998).

    Google Scholar 

  41. Kornberg, R. & Lorch, Y. Twenty-five years of the nucleosome, fundamental particle of the eukaryotic chromosome. Cell 98, 285–294 (1999).

    Article  CAS  Google Scholar 

  42. Thomas, G. J., Prescott, B. & Olins, D. E. Secondary structure of histones and DNA in chromatin. Science 197, 385–388 (1977).

    Article  CAS  Google Scholar 

  43. Mardian, J. K., Paton, A. E., Bunick, G. J. & Olins, D. E. Nucleosome cores have two specific binding sites for nonhistone chromosomal proteins HMG 14 and HMG 17. Science 209, 1534–1536 (1980).

    Article  CAS  Google Scholar 

  44. Sandeen, G., Wood, W. I. & Felsenfeld, G. The interaction of high mobility proteins HMG14 and 17 with nucleosomes. Nucl. Acids Res. 8, 3757–3778 (1980).

    Article  CAS  Google Scholar 

  45. Olins, D. E. et al. Electron microscope tomography: transcription in three dimensions. Science 220, 498–500 (1983).

    Article  CAS  Google Scholar 

  46. Olins, A. L., Olins, D. E. & Bazett-Jones, D. P. Balbiani ring hnRNP substructure visualized by selective staining and electron spectroscopic imaging. J. Cell Biol. 117, 483–491 (1992).

    Article  CAS  Google Scholar 

  47. Olins, D. E. & Olins, A. L. The replication band of ciliated protozoa. Int. Rev. Cytol. 153, 137–170 (1994).

    Article  CAS  Google Scholar 

  48. Richmond, T. J., Finch, J. T., Rushton, B., Rhodes, D. & Klug, A. Structure of the nucleosome core particle at 7 Å resolution. Nature 311, 532–537 (1984).

    Article  CAS  Google Scholar 

  49. 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 

  50. Uberbacher, E. C. & Bunick, G. J. X-ray structure of the nucleosome core particle. J. Biomol. Struct. Dyn. 2, 1033–1055 (1985).

    Article  CAS  Google Scholar 

  51. Harp, J. M., Hanson, B. L., Tim, D. E. & Bunick, G. J. Asymmetries in the nucleosome core particle at 2.5 Å resolution. Acta Crystallogr. (Section D Biol. Crystallogr.) 56, 1513–1534 (2000).

    Google Scholar 

  52. Harp, J. M., Hanson, B. L. & Bunick, G. J. The Structure of the Nucleosome Core Particle (Elsevier Science B. V., Amsterdam) (in the press).

  53. Arents, G., Burlingame, R. W., Wang, B. C., Love, W. E. & Moudrianakis, E. N. The nucleosomal core histone octamer at 3.1 Å resolution: a tripartite protein assembly and a left-handed superhelix. Proc. Natl Acad. Sci. USA 88, 10148–10152 (1991).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  56. Horn, P. J. & Peterson, C. L. Chromatin higher order folding: wrapping up transcription. Science 297, 1824–1827 (2002).

    Article  CAS  Google Scholar 

  57. de la Serna, I. L. & Imbalzano, A. N. Unfolding heterochromatin for replication. Nature Genet. 32, 560–562 (2002).

    Article  CAS  Google Scholar 

  58. Turner, B. M. Decoding the nucleosome. Cell 75, 5–8 (1993).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  60. Fry, C. J. & Peterson, C. L. Unlocking the gates to gene expression. Science 295, 1847–1848 (2002).

    Article  CAS  Google Scholar 

  61. Heun, P., Laroche, T., Shimada, K., Furrer, P. & Gasser, S. M. Chromosome dynamics in the yeast interphase nucleus. Science 294, 2181–2186 (2001).

    Article  CAS  Google Scholar 

  62. Hutchinson, C. Lamins: building blocks or regulators of gene expression. Nature Rev. Mol. Cell Biol. 3, 848–858 (2002).

    Article  Google Scholar 

  63. Burke, B. & Stewart, C. L. Life at the edge: the nuclear envelope and human disease. Nature Rev. Mol. Cell Biol. 3, 575–585 (2002).

    Article  CAS  Google Scholar 

  64. Hoffmann, K. et al. Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger–Huët anomaly). Nature Genet. 31, 410–414 (2002).

    Article  CAS  Google Scholar 

  65. Shultz, L. D. et al. Mutations at the mouse ichthyosis locus are within the lamin B receptor gene: a single gene model for human Pelger–Huët anomaly. Hum. Mol. Genet. 12, 61–69 (2003).

    Article  CAS  Google Scholar 

  66. Waterham, H. R. et al. Autosomal recessive HEM/Greenberg skeletal dysplasia is caused by 3β-hydroxysterol Δ14-reductase deficiency due to mutations in the lamin B receptor gene. Am. J. Hum. Genet. 72, 1013–1017 (2003).

    Article  CAS  Google Scholar 

  67. Grandville, J. J. Un Autre Monde (H. Fournier, Paris, 1844).

    Google Scholar 

  68. DuPraw, E. J. Quantitative constraints in the arrangement of human DNA. Cold Spring Harb. Symp. Quant. Biol. 38, 87–98 (1974).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors express their gratitude to Bowdoin College and to the German Cancer Research Center (Heidelberg) for providing stimulating intellectual and scientific environments. H. Herrmann and P. Lichter, our generous hosts at the German Cancer Research Center, supplied helpful comments on the manuscript. Several anonymous referees made significant contributions towards the improvement of this essay. The authors dedicate this review to the memory of H. G. Davis (formerly at the Department of Biophysics, King's College, London), an excellent microscopist and our good friend.

Author information

Authors and Affiliations

Authors

Related links

Related links

DATABASES

LocusLink

H2A

H2B

H3

H4

HMGN1

HMGN2

lamin A

lamin B1

lamin B2

LBR

OMIM

Emery–Dreifuss muscular dystrophy

Pelger–Huët anomaly

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Olins, D., Olins, A. Chromatin history: our view from the bridge. Nat Rev Mol Cell Biol 4, 809–814 (2003). https://doi.org/10.1038/nrm1225

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm1225

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