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.

  • Review Article
  • Published:

Chromatin as an expansive canvas for chemical biology

Abstract

Chromatin is extensively chemically modified and thereby acts as a dynamic signaling platform controlling gene function. Chromatin regulation is integral to cell differentiation, lineage commitment and organism development, whereas chromatin dysregulation can lead to age-related and neurodegenerative disorders as well as cancer. Investigating chromatin biology presents a unique challenge, as the issue spans many disciplines, including cell and systems biology, biochemistry and molecular biophysics. In recent years, the application of chemical biology methods for investigating chromatin processes has gained considerable traction. Indeed, chemical biologists now have at their disposal powerful chemical tools that allow chromatin biology to be scrutinized at the level of the cell all the way down to the single chromatin fiber. Here we present recent examples of how this rapidly expanding palette of chemical tools is being used to paint a detailed picture of chromatin function in organism development and disease.

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: Organization and analysis of chromatin.
Figure 2: Chemical synthesis of designer chromatin.
Figure 3: Small-molecule inhibitors of writers and erasers of histone marks.
Figure 4: Readout of histone marks.
Figure 5: Small-molecule inhibitors of histone-binding modules.
Figure 6: Control of chromatin function by histone marks through cis- and trans-acting mechanisms.

Similar content being viewed by others

References

  1. Woodcock, C.L. & Ghosh, R.P. Chromatin higher-order structure and dynamics. Cold Spring Harb. Perspect. Biol. 2, a000596 (2010).

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  3. Chi, P., Allis, C.D. & Wang, G.G. Covalent histone modifications–miswritten, misinterpreted and mis-erased in human cancers. Nat. Rev. Cancer 10, 457–469 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Cole, P.A. Chemical probes for histone-modifying enzymes. Nat. Chem. Biol. 4, 590–597 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Chatterjee, C. & Muir, T.W. Chemical approaches for studying histone modifications. J. Biol. Chem. 285, 11045–11050 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Filion, G.J. et al. Systematic protein location mapping reveals five principal chromatin types in Drosophila cells. Cell 143, 212–224 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Ernst, J. & Kellis, M. Discovery and characterization of chromatin states for systematic annotation of the human genome. Nat. Biotechnol. 28, 817–825 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Kharchenko, P.V. et al. Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature 471, 480–485 (2011).

    CAS  PubMed  Google Scholar 

  9. Taverna, S.D., Li, H., Ruthenburg, A.J., Allis, C.D. & Patel, D.J. How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nat. Struct. Mol. Biol. 14, 1025–1040 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Taunton, J., Hassig, C.A. & Schreiber, S.L. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 272, 408–411 (1996).

    CAS  PubMed  Google Scholar 

  11. Mund, C. & Lyko, F. Epigenetic cancer therapy: Proof of concept and remaining challenges. Bioessays 32, 949–957 (2010).

    CAS  PubMed  Google Scholar 

  12. Shahbazian, M.D. & Grunstein, M. Functions of site-specific histone acetylation and deacetylation. Annu. Rev. Biochem. 76, 75–100 (2007).

    CAS  PubMed  Google Scholar 

  13. Tóth, K.F. et al. Trichostatin A-induced histone acetylation causes decondensation of interphase chromatin. J. Cell Sci. 117, 4277–4287 (2004).

    PubMed  Google Scholar 

  14. Llères, D., James, J., Swift, S., Norman, D.G. & Lamond, A.I. Quantitative analysis of chromatin compaction in living cells using FLIM-FRET. J. Cell Biol. 187, 481–496 (2009).

    PubMed  PubMed Central  Google Scholar 

  15. Marks, P.A. & Breslow, R. Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat. Biotechnol. 25, 84–90 (2007).

    CAS  PubMed  Google Scholar 

  16. Huangfu, D. et al. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat. Biotechnol. 26, 795–797 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Sternson, S.M., Wong, J.C., Grozinger, C.M. & Schreiber, S.L. Synthesis of 7200 small molecules based on a substructural analysis of the histone deacetylase inhibitors trichostatin and trapoxin. Org. Lett. 3, 4239–4242 (2001).

    CAS  PubMed  Google Scholar 

  18. Bieliauskas, A.V. & Pflum, M.K.H. Isoform-selective histone deacetylase inhibitors. Chem. Soc. Rev. 37, 1402–1413 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Bradner, J.E. et al. Chemical phylogenetics of histone deacetylases. Nat. Chem. Biol. 6, 238–243 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Bantscheff, M. et al. Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nat. Biotechnol. 29, 255–265 (2011).

    CAS  PubMed  Google Scholar 

  21. Greiner, D., Bonaldi, T., Eskeland, R., Roemer, E. & Imhof, A. Identification of a specific inhibitor of the histone methyltransferase SU(VAR)3–9. Nat. Chem. Biol. 1, 143–145 (2005).

    CAS  PubMed  Google Scholar 

  22. McGarvey, K.M. et al. Silenced tumor suppressor genes reactivated by DNA demethylation do not return to a fully euchromatic chromatin state. Cancer Res. 66, 3541–3549 (2006).

    CAS  PubMed  Google Scholar 

  23. Kubicek, S. et al. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol. Cell 25, 473–481 (2007).

    CAS  PubMed  Google Scholar 

  24. Chang, Y. et al. Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294. Nat. Struct. Mol. Biol. 16, 312–317 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Vedadi, M. et al. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat. Chem. Biol. 7, 566–574 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Shi, Y. et al. A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell 2, 525–528 (2008).

    CAS  PubMed  Google Scholar 

  27. Min, J., Feng, Q., Li, Z.Z., Zhang, Y. & Xu, R.M. Structure of the catalytic domain of human Dot1L, a Non-SET domain nucleosomal histone methyltransferase. Cell 112, 711–723 (2003).

    CAS  PubMed  Google Scholar 

  28. Feng, Q. et al. Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain. Curr. Biol. 12, 1052–1058 (2002).

    CAS  PubMed  Google Scholar 

  29. Ng, H.H. et al. Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association. Genes Dev. 16, 1518–1527 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. van Leeuwen, F., Gafken, P.R. & Gottschling, D.E. Dot1p modulates silencing in yeast by methylation of the nucleosome core. Cell 109, 745–756 (2002).

    CAS  PubMed  Google Scholar 

  31. Okada, Y. et al. hDOT1L links histone methylation to leukemogenesis. Cell 121, 167–178 (2005).

    CAS  PubMed  Google Scholar 

  32. Krivtsov, A.V. et al. H3K79 methylation profiles define murine and human MLL-AF4 leukemias. Cancer Cell 14, 355–368 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Daigle, S.R. et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell 20, 53–65 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Bishop, A.C. et al. Design of allele-specific inhibitors to probe protein kinase signaling. Curr. Biol. 8, 257–266 (1998).

    CAS  PubMed  Google Scholar 

  35. Lin, Q., Jiang, F.Y., Schultz, P.G. & Gray, N.S. Design of allele-specific protein methyltransferase inhibitors. J. Am. Chem. Soc. 123, 11608–11613 (2001).

    CAS  PubMed  Google Scholar 

  36. Suganuma, T. & Workman, J.L. Signals and combinatorial functions of histone modifications. Annu. Rev. Biochem. 80, 473–499 (2011).

    CAS  PubMed  Google Scholar 

  37. Moazed, D. Mechanisms for the inheritance of chromatin states. Cell 146, 510–518 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Kim, J. et al. Tudor, MBT and chromo domains gauge the degree of lysine methylation. EMBO Rep. 7, 397–403 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Fischle, W., Franz, H., Jacobs, S.A., Allis, C.D. & Khorasanizadeh, S. Specificity of the chromodomain Y chromosome family of chromodomains for lysine-methylated ARK(S/T) motifs. J. Biol. Chem. 283, 19626–19635 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Fischle, W. et al. Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes Dev. 17, 1870–1881 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Fischle, W. et al. Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation. Nature 438, 1116–1122 (2005).

    CAS  PubMed  Google Scholar 

  42. Flanagan, J.F. et al. Double chromodomains cooperate to recognize the methylated histone H3 tail. Nature 438, 1181–1185 (2005).

    CAS  PubMed  Google Scholar 

  43. Ramón-Maiques, S. et al. The plant homeodomain finger of RAG2 recognizes histone H3 methylated at both lysine-4 and arginine-2. Proc. Natl. Acad. Sci. USA 104, 18993–18998 (2007).

    PubMed  Google Scholar 

  44. Garske, A.L., Craciun, G. & Denu, J.M. A combinatorial H4 tail library for exploring the histone code. Biochemistry 47, 8094–8102 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Garske, A.L. et al. Combinatorial profiling of chromatin binding modules reveals multisite discrimination. Nat. Chem. Biol. 6, 283–290 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Ruthenburg, A.J., Li, H., Patel, D.J. & Allis, C.D. Multivalent engagement of chromatin modifications by linked binding modules. Nat. Rev. Mol. Cell Biol. 8, 983–994 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Jacobson, R.H., Ladurner, A.G., King, D.S. & Tjian, R. Structure and function of a human TAFII250 double bromodomain module. Science 288, 1422–1425 (2000).

    CAS  PubMed  Google Scholar 

  48. Ruthenburg, A.J. et al. Recognition of a mononucleosomal histone modification pattern by BPTF via multivalent interactions. Cell 145, 692–706 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Schulze, W.X. & Mann, M. A novel proteomic screen for peptide-protein interactions. J. Biol. Chem. 279, 10756–10764 (2004).

    CAS  PubMed  Google Scholar 

  50. Vermeulen, M. et al. Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4. Cell 131, 58–69 (2007).

    CAS  PubMed  Google Scholar 

  51. Vermeulen, M. et al. Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers. Cell 142, 967–980 (2010).

    CAS  PubMed  Google Scholar 

  52. Bartke, T. et al. Nucleosome-interacting proteins regulated by DNA and histone methylation. Cell 143, 470–484 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Nikolov, M. et al. Chromatin affinity purification and quantitative mass spectrometry defining the interactome of histone modification patterns. Mol. Cell. Proteomics 10 (2011).

    Google Scholar 

  54. Shi, X. et al. ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Nature 442, 96–99 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Li, B. et al. Combined action of PHD and chromo domains directs the Rpd3S HDAC to transcribed chromatin. Science 316, 1050–1054 (2007).

    CAS  PubMed  Google Scholar 

  56. Zeng, L. et al. Mechanism and regulation of acetylated histone binding by the tandem PHD finger of DPF3b. Nature 466, 258–262 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Wells, J.A. & McClendon, C.L. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature 450, 1001–1009 (2007).

    CAS  PubMed  Google Scholar 

  58. Zeng, L. et al. Selective small molecules blocking HIV-1 Tat and coactivator PCAF association. J. Am. Chem. Soc. 127, 2376–2377 (2005).

    CAS  PubMed  Google Scholar 

  59. Sachchidanand et al. Target structure-based discovery of small molecules that block human p53 and CREB binding protein association. Chem. Biol. 13, 81–90 (2006).

    CAS  PubMed  Google Scholar 

  60. Borah, J.C. et al. A small molecule binding to the coactivator CREB-binding protein blocks apoptosis in cardiomyocytes. Chem. Biol. 18, 531–541 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Filippakopoulos, P. et al. Selective inhibition of BET bromodomains. Nature 468, 1067–1073 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Nicodeme, E. et al. Suppression of inflammation by a synthetic histone mimic. Nature 468, 1119–1123 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Morinière, J. et al. Cooperative binding of two acetylation marks on a histone tail by a single bromodomain. Nature 461, 664–668 (2009).

    PubMed  Google Scholar 

  64. Miyoshi, S., Ooike, S., Iwata, K., Hikawa, H. & Sugaraha, K. Antitumor agent. International patent PCT/JP2008/073864 (WO/2009/084693) (2009).

  65. Reynoird, N. et al. Oncogenesis by sequestration of CBP/p300 in transcriptionally inactive hyperacetylated chromatin domains. EMBO J. 29, 2943–2952 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Hargreaves, D.C., Horng, T. & Medzhitov, R. Control of inducible gene expression by signal-dependent transcriptional elongation. Cell 138, 129–145 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Herold, J.M. et al. Small-molecule ligands of methyl-lysine binding proteins. J. Med. Chem. 54, 2504–2511 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Li, S. & Shogren-Knaak, M.A. Cross-talk between histone H3 tails produces cooperative nucleosome acetylation. Proc. Natl. Acad. Sci. USA 105, 18243–18248 (2008).

    CAS  PubMed  Google Scholar 

  69. Li, S. & Shogren-Knaak, M.A. The Gcn5 bromodomain of the SAGA complex facilitates cooperative and cross-tail acetylation of nucleosomes. J. Biol. Chem. 284, 9411–9417 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Margueron, R. et al. Role of the polycomb protein EED in the propagation of repressive histone marks. Nature 461, 762–767 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Li, B. et al. Histone H3 lysine 36 dimethylation (H3K36me2) is sufficient to recruit the Rpd3s histone deacetylase complex and to repress spurious transcription. J. Biol. Chem. 284, 7970–7976 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Ng, H.H., Xu, R.M., Zhang, Y. & Struhl, K. Ubiquitination of histone H2B by Rad6 is required for efficient Dot1-mediated methylation of histone H3 lysine 79. J. Biol. Chem. 277, 34655–34657 (2002).

    CAS  PubMed  Google Scholar 

  73. McGinty, R.K., Kim, J., Chatterjee, C., Roeder, R.G. & Muir, T.W. Chemically ubiquitylated histone H2B stimulates hDot1L-mediated intranucleosomal methylation. Nature 453, 812–816 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. McGinty, R.K. et al. Structure activity analysis of semisynthetic nucleosomes: mechanistic insights into the stimulation of Dot1L by ubiquitylated histone H2B. ACS Chem. Biol. 4, 958–968 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Chatterjee, C., McGinty, R.K., Fierz, B. & Muir, T.W. Disulfide directed histone ubiquitylation reveals plasticity in hDot1L stimulation. Nat. Chem. Biol. 6, 267–269 (2010).

    CAS  PubMed  Google Scholar 

  76. Kim, J. et al. RAD6-Mediated transcription-coupled H2B ubiquitylation directly stimulates H3K4 methylation in human cells. Cell 137, 459–471 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Sun, Z.W. & Allis, C.D. Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature 418, 104–108 (2002).

    CAS  PubMed  Google Scholar 

  78. Canzio, D. et al. Chromodomain-mediated oligomerization of HP1 suggests a nucleosome-bridging mechanism for heterochromatin assembly. Mol. Cell 41, 67–81 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  80. Lu, X. et al. The effect of H3K79 dimethylation and H4K20 trimethylation on nucleosome and chromatin structure. Nat. Struct. Mol. Biol. 15, 1122–1124 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Fierz, B. et al. Histone H2B ubiquitylation disrupts local and higher-order chromatin compaction. Nat. Chem. Biol. 7, 113–119 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 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).

    CAS  PubMed  Google Scholar 

  83. Li, G. & Widom, J. Nucleosomes facilitate their own invasion. Nat. Struct. Mol. Biol. 11, 763–769 (2004).

    CAS  PubMed  Google Scholar 

  84. Gansen, A. et al. Nucleosome disassembly intermediates characterized by single-molecule FRET. Proc. Natl. Acad. Sci. USA 106, 15308–15313 (2009).

    CAS  PubMed  Google Scholar 

  85. Hall, M.A. et al. High-resolution dynamic mapping of histone-DNA interactions in a nucleosome. Nat. Struct. Mol. Biol. 16, 124–129 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Luger, K., Mader, A.W., Richmond, R.K., Sargent, D.F. & Richmond, T.J. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389, 251–260 (1997).

    CAS  PubMed  Google Scholar 

  87. Neumann, H. et al. A method for genetically installing site-specific acetylation in recombinant histones defines the effects of H3 K56 acetylation. Mol. Cell 36, 153–163 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Simon, M. et al. Histone fold modifications control nucleosome unwrapping and disassembly. Proc. Natl. Acad. Sci. USA 108, 12711–12716 (2011).

    CAS  PubMed  Google Scholar 

  89. Dawson, P.E., Muir, T.W., Clark-Lewis, I. & Kent, S.B.H. Synthesis of proteins by native chemical ligation. Science 266, 776–779 (1994).

    CAS  PubMed  Google Scholar 

  90. Muir, T.W., Sondhi, D. & Cole, P.A. Expressed protein ligation: a general method for protein engineering. Proc. Natl. Acad. Sci. USA 95, 6705–6710 (1998).

    CAS  PubMed  Google Scholar 

  91. Kee, J.M., Villani, B., Carpenter, L.R. & Muir, T.W. Development of stable phosphohistidine analogues. J. Am. Chem. Soc. 132, 14327–14329 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Moyle, P.M. & Muir, T.W. Method for the synthesis of mono-ADP-ribose conjugated peptides. J. Am. Chem. Soc. 132, 15878–15880 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Chatterjee, C., McGinty, R.K., Pellois, J.P. & Muir, T.W. Auxiliary-mediated site-specific peptide ubiquitylation. Angew. Chem. Int. Edn Engl. 46, 2814–2818 (2007).

    CAS  Google Scholar 

  94. Ajish Kumar, K.S., Haj-Yahya, M., Olschewski, D., Lashuel, H.A. & Brik, A. Highly efficient and chemoselective peptide ubiquitylation. Angew. Chem. Int. Edn Engl. 48, 8090–8094 (2009).

    CAS  Google Scholar 

  95. Simon, M.D. et al. The site-specific installation of methyl-lysine analogs into recombinant histones. Cell 128, 1003–1012 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Li, F. et al. A direct method for site-specific protein acetylation. Angew. Chem. Int. Edn Engl. 50, 9611–9614 (2011).

    CAS  Google Scholar 

  97. Neumann, H., Peak-Chew, S.Y. & Chin, J.W. Genetically encoding N-epsilon-acetyllysine in recombinant proteins. Nat. Chem. Biol. 4, 232–234 (2008).

    CAS  PubMed  Google Scholar 

  98. 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 

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

    CAS  PubMed  Google Scholar 

  100. Zheng, C. & Hayes, J.J. Intra- and inter-nucleosomal protein-DNA interactions of the core histone tail domains in a model system. J. Biol. Chem. 278, 24217–24224 (2003).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Some of the work discussed in this article was performed in the authors' group and was supported by the US National Institutes of Health and by the Swiss National Science Foundation, No. PA00P3-129130 (B.F.). We thank members of the Muir laboratory for critical reading of this article and apologize to the researchers whose work could not be cited because of space restraints.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tom W Muir.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fierz, B., Muir, T. Chromatin as an expansive canvas for chemical biology. Nat Chem Biol 8, 417–427 (2012). https://doi.org/10.1038/nchembio.938

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.938

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