Protein modules that manipulate histone tails for chromatin regulation

Nature Reviews Molecular Cell Biology

Volumn 2, Issue 6, 2001, Pages 422-432

  Marmorstein, Ronen ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HISTONE; NUCLEAR PROTEIN;

ANIMAL; CHEMISTRY; CHROMATIN; GENETIC TRANSCRIPTION; GENETICS; HUMAN; METABOLISM; PROTEIN BINDING; PROTEIN CONFORMATION; REVIEW; TRANSACTIVATION;

ANIMALS; CHROMATIN; HISTONES; HUMANS; NUCLEAR PROTEINS; PROTEIN BINDING; PROTEIN CONFORMATION; TRANS-ACTIVATION (GENETICS); TRANSCRIPTION, GENETIC;

EID: 0035377556     PISSN: 14710072     EISSN: None     Source Type: Journal    
DOI: 10.1038/35073047     Document Type: Review

References (117)

1. Wolffe, A. P. Chromatin: Structure and Function (Academic Press, London, 1992).
2. 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).
3. Bradbury, E. M. Reversible histone modifications and the chromosome cell cycle. BioEssays 14, 9-16 (1992).
4. Grunstein, M. Histone acetylation in chromatin structure and transcription. Nature 389, 349-352 (1997).
5. Thompson, J. S., Ling, X. & Grunstein, M. Histone H3 amino terminus is required for telomeric and silent mating locus repression in yeast. Nature 369, 245-247 (1994).
6. Durrin, L., Mann, R., Kayne, P. & Grunstein, M. Yeast histone H4 N-terminal sequence is required for promoter activation in vivo. Cell 65, 1023-1031 (1991).
7. Wolffe, A. P. & Hayes, J. J. Chromatin disruption and modification. Nucleic Acids Res. 27, 711-720 (1999).
8. Morales, V. & Richard-Foy, H. Role of histone N-terminal tails and their acetylation in nucleosome dynamics. Mol. Cell. Biol. 20, 7230-7237 (2000).
9. Hansen, J. C., Tse, C. & Wolffe, A. P. Structure and function of the core histone N-termini: more than meets the eye. Biochemistry 37, 17637-17641 (1998).
10. Sivolob, A., De Lucia, F., Alilat, M. & Prunell, A. Nucleosome dynamics. VI. Histone tail regulation of tetrasome chiral transition. A relaxation study of tetrasomes on DNA minicircles. J. Mol. Biol. 295, 55-69 (2000).
11. Wang, X., Moore, S. C., Laszckzak, M. & Ausio, J. Acetylation increases the α-helical content of the histone tails of the nucleosome. J. Biol. Chem. 275, 35013-35020 (2000).
12. Mutskov, V. et al. Persistent interactions of core histone tails with nucleosomal DNA following acetylation and transcription factor binding. Mol. Cell. Biol. 18, 6293-6304 (1998).
13. Polach, K. J., Lowary, P. T. & Widom, J. Effects of core histone tail domains on the equilibrium constants for dynamic DNA site accessibility in nucleosomes. J. Mol. Biol. 298, 211-223 (2000).
14. Turner, B. M. Histone acetylation as an epigenetic determinant of long-term transcriptional competence. Cell. Mol. Life Sci. 54, 21-31 (1998). The first to suggest that histone tail modifications may be histone marks that signal downstream transcriptional events.
15. Strahl, B. D. & Allis, C. D. The language of covalent histone modifications. Nature 403, 41-45 (2000). Builds on the initial proposal of Turner, to propose that distinct histone tail modifications provide a 'histone code' for downstream transcriptional activities.
16. Georgakopoulos, T. & Thireos, G. Two distinct yeast transcriptional activators require the function of the GCN5 protein to promote normal levels of transcription. EMBO J. 11, 4145-4152 (1992).
17. Marcus, G., Silverman, N., Berger, S., Horiuchi, J. & Guarente. L. Functional similarity and physical association between GCN5 and ADA2-putative transcriptional adaptors. EMBO J. 13, 4807-4815 (1994).
18. Horiuchi, J., Silverman, N., Marcus, G. A. & Guarente, L. ADA3, a putative transcriptional adaptor, consists of two separable domains and interacts with ADA2 and GCN5 in a trimeric complex. Mol. Cell. Biol. 15, 1203-1209 (1995).
19. Candau, R. & Berger, S. L. Structural and functional analysis of yeast putative adaptors: evidence for an adaptor complex in vivo. J. Biol. Chem. 271, 5237-5345 (1996).
20. Barlev, N. A. et al. Characterization of physical interactions of the putative transcriptional adaptor. ADA2, with acidic activation domains and TATA-binding protein. J. Biol. Chem. 270, 19337-19344 (1995).
21. Silverman, N., Agapite, J. & Guarente, L. Yeast ADA2 protein binds to the VP16 protein activation domain and activates transcription. Proc. Natl Acad. Sci. USA 91, 11665-11668 (1994).
22. Zamir, I. et al. A nuclear hormone receptor corepressor mediates transcriptional silencing by receptors with distinct repression domains. Mol. Cell. Biol. 16, 5458-5465 (1996).
23. Horlein, A. J. et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature 377, 397-404 (1995).
24. Kurokawa, R. et al. Polarity-specific activities of retinoic acid receptors determined by a co-repressor. Nature 377, 451-454 (1995).
25. Heinzel, T. et al. A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature 387, 43-48 (1997).
26. Alland, L. et al. Role for N-CoR and histone deacetylase in Sin3-mediated transcriptional repression. Nature 387, 49-55 (1997).
27. Pogo, B. G. T., Allfrey, V. G. & Mirsky, A. E. RNA synthesis and histone acetylation during the course of gene activation in lymphocytes. Proc. Natl Acad. Sci. USA 55, 6212-6222 (1966).
28. Vidali, G., Boffa, L. C., Bradbury, E. M. & Allfrey, V. G. Butyrate suppression of histone deacetylation leads to accumulation of multiacetylated forms of histones H3 and H4 and increased DNAase I sensitivity of the associated DNA sequences. Proc. Natl Acad. Sci. USA 75, 2239-2243 (1978).
29. Hebbes, T. R., Thorne, A. W. & Crane-Robinson, C. A direct link between core histone acetylation and transcriptionally active chromatin. EMBO J. 7, 1395-1403 (1988).
30. Hebbes, T. R., Clayton A. L. Throne A. W. & Crane-Robinson, C. Core histone hyperacetylation co-maps with generalized DNase I sensitivity in the chicken β-globin chromosomal domain. EMBO J. 13, 1823-1830 (1994).
31. Vettese-Dadey, M. et al. Acetylation of histone H4 plays a primary role in enhancing transcription factor binding to nucleosomal DNA in vitro. EMBO J 15, 2508-2518 (1996).
32. Sealy, L. & Chalkley, R. DNA associated with hyperacetylated histone is preferentially digested by DNase I. Nucleic Acids Res. 5, 1863-1876 (1978).
33. Brownell, J. E. et al. Tetrahymena histone acetyltransferase A: a homolog of yeast Gcn5p linking histone acetylation to gene activation. Cell 84, 843-851 (1996). The first to functionally link gene activation by a transcriptional co-activator to the histone acetyltransferase activity of that co-activator.
34. Berger, S. L. et al. Genetic isolation of ADA2: a potential transcriptional adaptor required for function of certain acidic activation domains. Cell 70, 251-265 (1992).
35. Wang, L., Liu, L. & Berger, S. L. Critical residues for histone acetylation by Gcn5, functioning in Ada and SAGA complexes, are also required for transcriptional function in vivo. Genes Dev. 12, 640-653 (1998).
36. Kuo, M. H., Zhou, J. X., Jambeck, P., Churchill, M. E. A. & Allis, C. D. Histone acetyltransferase activity of yeast Gcn5p is required for the activation of target genes in vivo. Genes Dev. 12, 627-639 (1998).
37. Shikama, N., Lyon, J. & LaThangue, N. B. The p300/CBP family: integrating signals with transcription factors and chromatin. Trends Cell Biol. 7, 230-236 (1997).
38. Bannister, A. J. & Kouzarides, T. The CBP co-activator is a histone acetyltransferase. Nature 384, 641-643 (1996).
39. 1250 subunit of TFIID has histone acetyltransferase activity. Cell 87, 1261-1270 (1996).
40. Cress, W. D. & Seto, E. Histone deacetylases, transcriptional control, and cancer. J. Cell. Physiol. 184, 1-16 (2000).
41. Kuo, M. H. & Allis, C. D. Roles of histone acetyltransferases and deacetylases in gene regulation. Bioessays 20, 615-626 (1998).
42. Neal, K. C., Pannuti, A., Smith, E. R. & Lucchesi, J. C. A new human member of the MYST family of histone acetyl transferases with high sequence similarity to Drosophila MOF. Biochim. Biophys. Acta 1490, 170-174 (2000).
43. Sterner, D. E. & Berger, S. L. Acetylation of histones and transcription-related factors. Microbiol. Mol. Biol. Rev. 64, 435-459 (2000).
44. Kawasaki, H. et al. ATF-2 has intrinsic histone acetyltransferase activity which is modulated by phosphorylation. Nature 405, 195-200 (2000).
45. Takechi, S. & Nakayama, T. Sas3 is a histone acetyltransferase and requires a zinc finger motif. Biochem. Biophys. Res. Commun. 266, 405-410 (1999).
46. EhrenhoferMurray, A. E., Rivier, D. H. & Rine, J. The role of Sas2, an acetyltransferase homologue of Saccharomyces cerevisiae, in silencing and ORC function. Genetics 145, 923-934 (1997).
47. Kuo, M. H. et al. Transcription-linked acetylation by Gcn5p of histones H3 and H4 at specific lysines. Nature 383, 269-272 (1996).
48. Trievel, R. C., Li, F.-Y. & Marmorstein, R. Application of a novel fluorescence histone acetyltransferase enzyme assay to study the substrate specificity of human PCAF. Anal. Biochem. 287, 319-328 (2000).
49. 130-containing HAT complex that interacts with the Spt16 subunit of the yeast CP (Cdc68/Pob3)-FACT complex. Genes Dev. 14, 1196-1208 (2000).
50. Ogryzko, V. V., Schiltz, R. L., Russanova, V., Howard, B. H. & Nakatani, Y. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 87, 953-959 (1996).
51. Grant, P. A. et al. Yeast Gcn5 functions in two multisubunit complexes to acetylate nucleosomal histones: characterization of an Ada complex and the SAGA (Spt/Ada) complex. Genes Dev. 11, 1640-1650 (1997).
52. Allard, S. et al. NuA4, an essential transcription adaptor/histone H4 acetyltransferase complex containing Esa1 p and the ATM-related cofactor Tra1p. EMBO J. 18, 5108-5119 (1999).
53. Grant, P. A. et al. Expanded lysine acetylation specificity of Gcn5 in native complexes. J. Biol. Chem. 274, 5895-5900 (1999).
54. Trievel, R. C. et al. Crystal structure and mechanism of histone acetylation of the yeast GCN5 transcriptional coactivator. Proc. Natl Acad. Sci. USA 96, 8931-8936 (1999).
55. Clements, A. et al. Crystal structure of the histone acetyltransferase domain of the human P/CAF transcriptional regulator bound to coenzyme-A. EMBO J. 18, 3521-3532 (1999).
56. Rojas, J. R. et al. Structure of the Tetrahymena GCN5 bound to coenzyme-A and a histone H3 peptide. Nature 401, 93-98 (1999). Revealed the first high-resolution structure of a HAT bound to a histone peptide substrate.
57. Un, Y., Fletcher, C. M., Zhou, J., Allis, C. D. & Wagner, G. Solution structure of the catalytic domain of Tetrahymena GCN5 histone acetyltransferase in complex with coenzyme A. Nature 400, 86-89 (1999).
58. Yan, Y., Bariev, N. A., Haley, R. H., Berger, S. L. & Marmorstein, R. Crystal structure of yeast Esa1 suggests a unified mechanism of catalysis and substrate binding by histone acetyltransferases. Mol. Cell 6, 1195-1205 (2000).
59. Dutnall, R. N., Tafrov, S. T., Sternglanz, R. & Ramakrishnan, V. Structure of the histone acetyltransferase Hat1: a paradigm for the GCN5-related N-acetyltransferase superfamily. Cell 94, 427-438 (1998).
60. Jeanmougin, F., Wurtz, J. M., LeDouarin, B., Chambon, P. & Losson, R. The bromodomain revisited. Trends Biochem. Sci. 22, 151-153 (1997).
61. Winston, F. & Allis, C. D. The bromodomain: a chromatin-targeting module? Nature Struct. Biol. 6, 601-604 (1999).
62. Sterner, D. E. et al. Functional organization of the yeast SAGA complex: distinct components involved in structural integrity, nucleosome acetylation, and TATA-binding protein interaction. Mol. Cell. Biol. 19, 86-98 (1999).
63. Kraus, W. L., Manning, E. T. & Kadonaga, J. T. Biochemical analysis of distinct activation functions in p300 that enhance transcription initiation with chromatin templates. Mol. Cell. Biol. 19, 8123-8135 (1999).
64. Du, J., Nasir, I., Benton, B. K., Kladde, M. P. & Laurent, B. C. Sth1p, a Saccharomyces cerevisiae Snf2p/Swi2p homolog, is an essential ATPase in RSC and differs from Snf/Swi in its interactions with histones and chromatin-associated proteins. Genetics 150, 987-1005 (1998).
65. Matangkasombut, O., Buratowski, R. M., Swilling, N. W. & Buratowski, S. Bromodomain factor 1 corresponds to a missing piece of yeast TFIID. Genes Dev 14, 951-962 (2000).
66. Ornaghi, P., Ballario, P., Lena, A. M., Gonzalez, A. & Filetici, P. The bromodomain of Gcn5p interacts in vitro with specific residues in the N terminus of histone H4. J. Mol. Biol. 287, 1-7 (1999).
67. Dhalluin, C. et al. Structure and ligand of a histone acetyltransferase bromodomain. Nature 399, 491-496 (1999). Provided the first evidence that bromodomains specifically target acetyl-lysine-containing histone substrates.
68. 1250 double bromodomain module. Science 288, 1422-1425 (2000).
69. Owen, D. J. et al. The structural basis for the recognition of acetylated histone H4 by the bromodomain of histone acetyltransferase Gcn5p. EMBO J. 19, 6141-6149 (2000).
70. Clayton, A. L., Rose, S., Barratt, M. J. & Mahadevan, L. C. Phosphoacetylation of histone H3 on c-fos- and c-jun-associated nucleosomes upon gene activation. EMBO J. 19, 3714-3726 (2000).
71. Nowak, S. J. & Corces, V. G. Phosphorylation of histone H3 correlates with transcriptionally active loci. Genes Dev. 14, 3003-3013 (2000).
72. Cheung, P. et al. Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation. Mol. Cell 5, 905-915 (2000).
73. Lo, W.-S. et al. Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14. Mol. Cell 5, 917-926 (2000). References 72 and 73 revealed that Ser10 phosphorylation of histone H3 is functionally linked to histone acetylation at Lys14 and to gene activation of a subset of Gcn5-dependent genes.
74. Hsu, J. Y. et al. Mitotic phosphorylation of histone H3 is governed by IpI1/Aurora kinase and GIC7/PP1 phosphatase in budding yeast and nematodes. Cell 102, 279-291 (2000).
75. De Souza, C. P., Osmani, A. H., Wu, L. P., Spotts, J. L. & Osmani, S. A. Mitotic histone H3 phosphorylation by the NIMA kinase in Aspergillus nidulans. Cell 102, 293-302 (2000). References 74 and 75 indicate that phosphorylation of histone H3 at Ser 10 is mediated by the IpI1/Aurora kinase and that this activity is functionally linked to chromosome condensation during mitosis.
76. Hassan, A. H., Neely, K. E. & Workman, J. L. Histone acetyltransferase complexes stabilize swi/snf binding to promoter nucleosomes. Cell 104, 817-827 (2001).
77. Cosma, M. P., Tanaka, T. & Nasmyth, K. Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle- and developmentally regulated promoter. Cell 97, 299-311 (1999).
78. Krebs, J. E., Fry, C. J., Samuels, M. L. & Peterson, C. L. Global role for chromatin remodeling enzymes in mitotic gene expression. Cell 102, 587-593 (2000). References 76-78 indicate a functional link between histone acetylation and chromatin remodelling.
79. Weiler, K. S. & Wakimoto, B. T. Heterochromatin and gene expression in Drosophila. Annu. Rev. Genet. 29, 577-605 (1995).
80. Grunstein, M. Molecular model for telomeric heterochromatin in yeast. Curr. Opin. Cell Biol. 9, 383-387 (1997).
81. Reuter, G. & Spierer, P. Position effect variegation and chromatin proteins. Bioessays 14, 605-612 (1992).
82. Allshire, R. C., Nimmo, E. R., Ekwall, K., Javerzat, J. P. & Cranston, G. Mutations derepressing silent centromeric domains in fission yeast disrupt chromosome segregation. Genes Dev. 9, 218-233 (1995).
83. Schotta, G. & Reuter, G. Controlled expression of tagged proteins in Drosophila using a new modular P-element vector system. Mol. Gen. Genet. 262, 916-920 (2000).
84. Tschiersch, B. et al. The protein encoded by the Drosophila position-effect variegation suppressor gene Su(var)3-9 combines domains of antagonistic regulators of homeotic gene complexes. EMBO J. 13, 3822-3831 (1994).
85. Rea, S. et al. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406, 593-599 (2000). Shows that suppressors of variegation gene product, Su(var)3-9, mediates gene silencing through its histone H3 methyltransferase activity.
86. Jenuwein, T., Laible, G., Dorn, R. & Reuter, G. SET domain proteins modulate chromatin domains in eu- and heterochromatin. Cell. Mol. Life Sci. 54, 80-93 (1998).
87. Bannister, A. J. et al. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 401, 120-124 (2001).
88. Lachner, M., O'Carroll, D., Rea, S., Mechtler, K. & Jenuwein, T. Methytation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 401, 116-120 (2001). References 87 and 88 indicate that the chromodomain of the heterochromatin-associated protein, HP1, targets the Lys9 of histone H3 for heterochromatin assembly and gene silencing.
89. Eissenberg, J. C. et al. Mutation in a heterochromatin-specific chromosomal protein is associated with suppression of position-effect variegation in Drosophila melanogaster. Proc. Natl Acad. Sci. USA 87, 9923-9927 (1990).
90. Nakayama, J., Rice, J. C., Strahl, B. D., Allis, C. D. & Grewal, S. I. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 292, 110-113 (2001).
91. Akhtar, A., Zink, D. & Becker, P. B. Chromodomains are protein-RNA interaction modules. Nature 407, 405-409 (2000).
92. Ball, L. J. et al. Structure of the chromatin binding (chromo) domain from mouse modifier protein 1. EMBO J. 16, 2473-2481 (1997). Provides the first atomic structure of a chromodomain.
93. Platero, J. S., Hartnett, T. & Eissenberg, J. C. Functional analysis of the chromo domain of HP1. EMBO J. 14, 3977-3986 (1995).
94. Edmondson, S. P., Qiu, L. & Shriver, J. W. Solution structure of the DNA-binding protein Sac7d from the hyperthermophile Sulfolobus acidocaldarius. Biochemistry 34, 13289-133304 (1995).
95. Baumann, H., Knapp, S., Lundback, T., Ladenstein, R. & Hard, T. Solution structure and DNA-binding properties of a thermostable protein from the archaeon Sulfolobus solfataricus. Nature Struct. Biol. 1, 808-819 (1994).
96. Aasland, R. & Stewart, A. F. The chrome shadow domain, a second chrome domain in heterochromatin-binding protein-1, HP1. Nucleic Acids Res. 23, 3168-3173 (1995).
97. Fanti, L., Giovinazzo, G., Berloco, M. &, Pimpinelli, S. The heterochromatin protein 1 prevents telomere fusions in Drosophila. Mol. Cell 2, 527-538 (1998).
98. Murzina, N., Verreault, A., Laue, E. & Stillman, B. Heterochomatin dynamics in mouse cells: interaction between chromatin assembly factor 1 and HP1 proteins. Mol. Cell 4, 529-540 (1999).
99. Smothers, J. F. & Henikoff, S. The HP1 chromo shadow domain binds a consensus peptide pentamer. Curr. Biol. 10, 27-30 (2000).
100. Brasher, S. V. et al. The structure of mouse HP1 suggests a unique mode of single peptide recognition by the shadow chrome domain dimer. EMBO J. 19, 1587-1597 (2000). Provides the first atomic structure of a chromoshadow domain.
101. Strahl, B. D., Ohba, R., Cook, R. G. & Allis, C. D. Methylation of histone H3 at lysine 4 is highly conserved and correlates with transcriptionally active nuclei in Tetrahymena. Proc. Natl Acad. Sci. USA 96, 14967-14972 (1999). Indicates that histone methylation can be correlated with gene activation.
102. Chen, D. et al. Regulation of transcription by a protein methyltransferase. Science 284, 2174-2177 (1999).
103. Stallcup, M. R. et al. Co-operation between protein-acetylating and protein-methylating co-activators in transcriptional activation. Biochem. Soc. Trans. 28, 415-418 (2000).
104. Travers, A. An engine for nucleosome remodeling. Cell 96, 311-314 (1999).
105. Cartson, M. & Laurent, B. C. The SNF/SW1 family of global transcriptional activators. Curr. Opin. Cell Biol. 6, 396-402 (1994).
106. Peterson, C. L. & Tamkun, J. W. The SWI-SNF complex: a chromatin remodeling machine? Trends Biochem. Sci. 20, 143-146 (1995).
107. Ng, H. H. & Bird, A. Histone deacetylases: silencers for hire. Trends Biochem. Sci. 25, 121-126 (2000).
108. Kouzarides, T. Histone acetylases and deacetylases in cell proliferation. Curr Opin Genet. Dev. 9, 40-48 (1999).
109. Xue, Y. et al. NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Mol. Cell 2, 851-861 (1998). Describes a transcriptional regulatory complex that has both histone deacetylase and chromatin remodelling activity, indicating a direct link between the histone acetylation status and chromatin remodelling.
110. Borden, K. L. RING domains: master builders of molecular scaffolds? J. Mol. Biol. 295, 1103-1112 (2000).
111. Aasland, R., Gibson, T. J. & Stewart, A. F. The PHD finger: implications for chromatin-mediated transcriptional regulation. Trends Biochem. Sci. 20, 56-59 (1995).
112. Jackson, P. K. et al. The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases. Trends Cell Biol. 10, 429-439 (2000).
113. Aasland, R., Stewart, A. F. & Gibson, T. The SANT domain: a putative DNA-binding domain in the SWI-SNF and ADA complexes, the transcriptional corepressor N-CoR and TFIIIB. Trends Biochem. Sci. 21, 87-88 (1996).
114. Sullivan, S. A., Aravind, L., Makalowski, I., Baxevanis, A. D. & Landsman, D. The histone database: a comprehensive WWW resource for histories and histone fold-containing proteins. Nucleic Acids Res. 28, 320-322 (2000).
115. Burley, S. K. & Roeder, R. G. Biochemistry and structural biology of transcription factor IID (TFIID). Annu. Rev. Biochem. 65, 769-799 (1996).
116. Xie, X. et al. Structural similarity between TAFs and the heterotetrameric core of the histone octamer. Nature 380, 316-322 (1996).
117. Luger, K., Mader, A. W., Richmond, R. K., Sargent, D. F. & Richmond, T. J. Crystal structure of the nucleosome core particle at 2.8 angstrom resolution. Nature 389, 251-260 (1997). Describes the atomic structure of the nucleosome core particle indicating that, at least in the context of the core particle, the histone tail regions are largely disordered.