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Defining an epigenetic code

Nature Cell Biology volume 9, pages 2–6 (2007)Cite this article

The nucleosome surface is decorated with an array of enzyme-catalysed modifications on histone tails. These modifications have well-defined roles in a variety of ongoing chromatin functions, often by acting as receptors for non-histone proteins, but their longer-term effects are less clear. Here, an attempt is made to define how histone modifications operate as part of a predictive and heritable epigenetic code that specifies patterns of gene expression through differentiation and development.

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Figure 1: Histone modifications can generate both short-term and long-term outcomes.
Figure 2: A hypothetical illustration of how an epigenetic code may work in the pre-implantation embryo.

References

  1. 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).

    Article  CAS  Google Scholar 

  2. Margueron, R., Trojer, P. & Reinberg, D. The key to development: interpreting the histone code? Curr. Opin. Genet. Dev. 15, 163–176 (2005).

    Article  CAS  Google Scholar 

  3. Nightingale, K. P., O'Neill, L. P. & Turner, B. M. Histone modifications: signalling receptors and potential elements of a heritable epigenetic code. Curr. Opin. Genet. Dev. 16, 125–136 (2006).

    Article  CAS  Google Scholar 

  4. Turner, B. M., Birley, A. J. & Lavender, J. Histone H4 isoforms acetylated at specific lysine residues define individual chromosomes and chromatin domains in Drosophila polytene nuclei. Cell 69, 375–384 (1992).

    Article  CAS  Google Scholar 

  5. Hazzalin, C. A. & Mahadevan, L. C. Dynamic acetylation of all lysine 4-methylated histone H3 in the mouse nucleus: analysis at c-fos and c-jun. PLoS Biol. 3, e393 (2005).

    Article  Google Scholar 

  6. Metivier, R. et al. Estrogen receptor-α directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell 115, 751–763 (2003).

    Article  CAS  Google Scholar 

  7. Schreiber, S. L. & Bernstein, B. E. Signaling network model of chromatin. Cell 111, 771–778 (2002).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Mateescu, B., England, P., Halgand, F., Yaniv, M. & Muchardt, C. Tethering of HP1 proteins to chromatin is relieved by phosphoacetylation of histone H3. EMBO Rep. 5, 490–496 (2004).

    Article  CAS  Google Scholar 

  10. Hake, S. B. & Allis, C. D. Histone H3 variants and their potential role in indexing mammalian genomes: the “H3 barcode hypothesis”. Proc. Natl Acad. Sci. USA 103, 6428–6435 (2006).

    Article  CAS  Google Scholar 

  11. Peters, A. H. et al. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol. Cell 12, 1577–1589 (2003).

    Article  CAS  Google Scholar 

  12. Heard, E. Delving into the diversity of facultative heterochromatin: the epigenetics of the inactive X chromosome. Curr. Opin. Genet. Dev. 15, 482–489 (2005).

    Article  CAS  Google Scholar 

  13. Barbieri, M. The Organic Codes; An Introduction to Semantic Biology (Cambridge University Press, Cambridge, 2003).

    Google Scholar 

  14. Segal, E. et al. A genomic code for nucleosome positioning. Nature 442, 772–778 (2006).

    Article  CAS  Google Scholar 

  15. Crick, F. H. On the genetic code. Science 139, 461–464 (1963).

    Article  CAS  Google Scholar 

  16. Crick, F. H. The recent excitement in the coding problem. Progress in Nucleic Acid Research 1, 163–217 (1963).

    Article  CAS  Google Scholar 

  17. Dion, M. F., Altschuler, S. J., Wu, L. F. & Rando, O. J. Genomic characterization reveals a simple histone H4 acetylation code. Proc. Natl Acad. Sci. USA 102, 5501–5506 (2005).

    Article  CAS  Google Scholar 

  18. Liu, C. L. et al. Single-nucleosome mapping of histone modifications in S. cerevisiae. PLoS Biol. 3, e328 (2005).

    Article  Google Scholar 

  19. Bird, A. DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6–21 (2002).

    Article  CAS  Google Scholar 

  20. Jaenisch, R. & Bird, A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nature Genet 33, 245–254 (2003).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  22. Wilson, C. B. & Merkenschlager, M. Chromatin structure and gene regulation in T cell development and function. Curr. Opin. Immunol. 18, 143–151 (2006).

    Article  CAS  Google Scholar 

  23. Gilbert, N., Gilchrist, S. & Bickmore, W. A. Chromatin organization in the mammalian nucleus. Int. Rev. Cytol. 242, 283–336 (2005).

    Article  CAS  Google Scholar 

  24. Sproul, D., Gilbert, N. & Bickmore, W. A. The role of chromatin structure in regulating the expression of clustered genes. Nature Rev. Genet. 6, 775–781 (2005).

    Article  CAS  Google Scholar 

  25. Ringrose, L. & Paro, R. Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu. Rev. Genet. 38, 413–443 (2004).

    Article  CAS  Google Scholar 

  26. Ralston, A. & Rossant, J. Genetic regulation of stem cell origins in the mouse embryo. Clin. Genet. 68, 106–112 (2005).

    Article  CAS  Google Scholar 

  27. Szutorisz, H. et al. Formation of an active tissue-specific chromatin domain initiated by epigenetic marking at the embryonic stem cell stage. Mol. Cell Biol. 25, 1804–1820 (2005).

    Article  CAS  Google Scholar 

  28. Szutorisz, H. & Dillon, N. The epigenetic basis for embryonic stem cell pluripotency. Bioessays 27, 1286–1293 (2005).

    Article  CAS  Google Scholar 

  29. Chambeyron, S. & Bickmore, W. A. Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription. Genes Dev. 18, 1119–1130 (2004).

    Article  CAS  Google Scholar 

  30. Wysocka, J. et al. A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling. Nature 442, 86–90 (2006).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

I am grateful to M. Barbieri for drawing my attention to the world of semiotics, and to A. Ferguson-Smith and colleagues in the Chromatin and Gene Expression Group for their thoughts, criticisms and insights.

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  1. Institute of Biomedical Research, University of Birmingham Medical School, Birmingham, B15 2TT, UK

    Bryan M. Turner

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  1. Bryan M. Turner
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Turner, B. Defining an epigenetic code. Nat Cell Biol 9, 2–6 (2007). https://doi.org/10.1038/ncb0107-2

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