Abstract
The 1.9-Å-resolution crystal structure of the nucleosome core particle containing 147 DNA base pairs reveals the conformation of nucleosomal DNA with unprecedented accuracy. The DNA structure is remarkably different from that in oligonucleotides and non-histone protein–DNA complexes. The DNA base-pair-step geometry has, overall, twice the curvature necessary to accommodate the DNA superhelical path in the nucleosome. DNA segments bent into the minor groove are either kinked or alternately shifted. The unusual DNA conformational parameters induced by the binding of histone protein have implications for sequence-dependent protein recognition and nucleosome positioning and mobility. Comparison of the 147-base-pair structure with two 146-base-pair structures reveals alterations in DNA twist that are evidently common in bulk chromatin, and which are of probable importance for chromatin fibre formation and chromatin remodelling.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
van Holde, K. E. in Chromatin (ed. Rich, A.) (Springer, New York, 1988)
Kornberg, R. D. & Lorch, Y. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98, 285–294 (1999)
Elgin, S. C. R. & Workman, J. L. (eds) Chromatin Structure and Gene Expression (Oxford Univ. Press, Oxford, 2000)
Simpson, R. T. Nucleosome positioning: Occurrence, mechanisms, and functional consequences. Prog. Nucleic Acid Res. Mol. Biol. 40, 143–184 (1991)
Wolffe, A. P. & Kurumizaka, H. The nucleosome: A powerful regulator of transcription. Prog. Nucleic Acid Res. Mol. Biol. 61, 379–422 (1998)
Wyrick, J. J. et al. Chromosomal landscape of nucleosome-dependent gene expression and silencing in yeast. Nature 402, 418–421 (1999)
Luger, K., Maeder, 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)
Pryciak, P. M. & Varmus, H. E. Nucleosomes, DNA-binding proteins, and DNA sequence modulate retroviral integration target site selection. Cell 69, 769–780 (1992)
Kornberg, R. D. & Lorch, Y. Chromatin structure and transcription. Annu. Rev. Cell Biol. 8, 563–587 (1992)
Shimizu, M., Roth, S. Y., Szent-Gyorgyi, C. & Simpson, R. T. Nucleosomes are positioned with base pair precision adjacent to the alpha 2 operator in Saccharomyces cerevisiae. EMBO J. 10, 3033–3041 (1991)
Flaus, A. & Richmond, T. J. Positioning and stability of nucleosomes on MMTV 3′LTR sequences. J. Mol. Biol. 275, 427–441 (1998)
Meersseman, G., Pennings, S. & Bradbury, E. M. Mobile nucleosomes—a general behaviour. EMBO J. 11, 2951–2959 (1992)
Polach, K. J. & Widom, J. Mechanism of protein access to specific DNA sequences in chromatin: A dynamic equilibrium model for gene regulation. J. Mol. Biol. 254, 130–149 (1995)
Studitsky, V. M., Kassavetis, G. A., Geiduschek, E. P. & Felsenfeld, G. Mechanism of transcription through the nucleosome by eukaryotic RNA polymerase. Science 278, 1960–1963 (1997)
Tsukiyama, T. The in vivo functions of ATP-dependent chromatin-remodelling factors. Nature Rev. Mol. Cell Biol. 3, 422–429 (2002)
Calladine, C. R. & Drew, H. R. Principles of sequence-dependent flexure of DNA. J. Mol. Biol. 192, 907–918 (1986)
Davey, C. A., Sargent, D. F., Luger, K., Maeder, A. W. & Richmond, T. J. Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 Å resolution. J. Mol. Biol. 319, 1097–1113 (2002)
Davey, C. A. & Richmond, T. J. DNA-dependent divalent cation binding in the nucleosome core particle. Proc. Natl Acad. Sci. USA 99, 11169–11175 (2002)
Crick, F. H. C. & Klug, A. Kinky helix. Nature 255, 530–533 (1975)
El Hassan, M. A. & Calladine, C. R. Conformational characteristics of DNA: Empirical classifications and a hypothesis for the conformational behaviour of dinucleotide steps. Phil. Trans. R. Soc. Lond. A 355, 43–100 (1997)
Lavery, R. & Sklenar, H. The definition of generalised helicoidal parameters and of axis curvature for irregular nucleic acids. J. Biomol. Struct. Dynam. 6, 63–91 (1988)
Young, M. A., Ravishanker, G., Beveridge, D. L. & Berman, H. M. Analysis of local helix bending in crystal structures of DNA oligonucleotides and DNA–protein complexes. Biophys. J. 68, 2454–2468 (1995)
Olson, W. K. Simulating DNA at low resolution. Curr. Opin. Struct. Biol. 6, 242–256 (1996)
Dickerson, R. E. DNA bending: The prevalence of kinkiness and the virtues of normality. Nucleic Acids Res. 26, 1906–1926 (1998)
Goodsell, D. S. & Dickerson, R. E. Bending and curvature calculations in B-DNA. Nucleic Acids Res. 22, 5497–5503 (1994)
El Hassan, M. A. & Calladine, C. R. Two distinct modes of protein-induced bending in DNA. J. Mol. Biol. 282, 331–343 (1998)
Packer, M. J. & Hunter, C. A. Sequence–structure relationships in DNA oligomers: A computational approach. J. Am. Chem. Soc. 123, 7399–7406 (2001)
Yanagi, K., Prive, G. G. & Dickerson, R. E. Analysis of local helix geometry in three B-DNA decamers and eight dodecamers. J. Mol. Biol. 217, 201–214 (1991)
Shrader, T. E. & Crothers, D. M. Effects of DNA sequence and histone–histone interactions on nucleosome placement. J. Mol. Biol. 216, 69–84 (1990)
Anselmi, C., Bocchinfuso, G., De Santis, P., Savino, M. & Scipioni, A. Dual role of DNA intrinsic curvature and flexibility in determining nucleosome stability. J. Mol. Biol. 286, 1293–1301 (1999)
Dickerson, R. E. & Chiu, T. K. Helix bending as a factor in protein/DNA recognition. Biopolymers 44, 361–403 (1997)
Packer, M. J. & Hunter, C. A. Sequence-dependent DNA structure: The role of the sugar-phosphate backbone. J. Mol. Biol. 280, 407–420 (1998)
Fratini, A. V., Kopka, M. L., Drew, H. R. & Dickerson, R. E. Reversible bending and helix geometry in a B-DNA dodecamer: CGCGAATTBrCGCG. J. Biol. Chem. 257, 14686–14707 (1982)
Olson, W. K., Gorin, A. A., Lu, X. J., Hock, L. M. & Zhurkin, V. B. DNA sequence-dependent deformability deduced from protein–DNA crystal complexes. Proc. Natl Acad. Sci. USA 95, 11163–11168 (1998)
Travers, A. A. & Klug, A. The bending of DNA in nucleosomes and its wider implications. Phil. Trans. R. Soc. Lond. B 317, 537–561 (1987)
Richmond, T. J. & Widom, J. in Chromatin Structure and Gene Expression (eds Elgin, S. C. R. & Workman, J. L.) 1–23 (Oxford Univ. Press, Oxford, 2000)
Widom, J. Role of DNA sequence in nucleosome stability and dynamics. Q. Rev. Biophys. 34, 269–324 (2001)
Zivanovic, Y., Goulet, I., Revet, B., Le Bret, M. & Prunell, A. Chromatin reconstitution on small DNA rings II. DNA supercoiling on the nucleosome. J. Mol. Biol. 200, 267–290 (1988)
Klug, A. & Lutter, L. C. The helical periodicity of DNA on the nucleosome. Nucleic Acids Res. 9, 4267–4283 (1981)
Arnott, S., Dover, S. D. & Wonacott, A. J. Least-squares refinement of the crystal and molecular structures of DNA and RNA from X-ray data and standard bond lengths and angles. Acta Crystallogr. B 25, 2192–2206 (1969)
Acknowledgements
We thank I. Berger and D. Sargent for comments on the manuscript. This study was supported by the Swiss National Science Fund.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare that they have no competing financial interests.
Supplementary information
41586_2003_BFnature01595_MOESM2_ESM.doc
Supplementary Methods: Calculation of DNA curvature, base pair and base-pair-step parameters, and backbone geometry. (DOC 28 kb)
41586_2003_BFnature01595_MOESM4_ESM.doc
Supplementary Tables: 1.) DNA mean conformational parameters. 2.) Principle components of DNA conformational parameters. 3.) Deviation of DNA phosphate group position for homologous histone motifs. (DOC 86 kb)
Rights and permissions
About this article
Cite this article
Richmond, T., Davey, C. The structure of DNA in the nucleosome core. Nature 423, 145–150 (2003). https://doi.org/10.1038/nature01595
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/nature01595
This article is cited by
-
Satellitome analyses in nematodes illuminate complex species history and show conserved features in satellite DNAs
BMC Biology (2022)
-
Generating specificity in genome regulation through transcription factor sensitivity to chromatin
Nature Reviews Genetics (2022)
-
Chemical map-based prediction of nucleosome positioning using the Bioconductor package nuCpos
BMC Bioinformatics (2021)
-
Hi-CO: 3D genome structure analysis with nucleosome resolution
Nature Protocols (2021)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.