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 structure and the inheritance of epigenetic information

Key Points

  • The chromatin landscape is a key aspect of epigenetic regulation in eukaryotes.

  • Old histones are recycled during DNA replication, therefore providing a blueprint for the duplication of their modifications following DNA replication.

  • Positive-feedback loops and cooperativity among chromatin-modifying complexes are crucial for the propagation of histone marks.

  • The nuclear architecture and long-range interactions are likely to contribute to inheritance of epigenetic information.

  • The concerted action of trans-acting factors and the chromatin landscape dictate the inheritance of epigenetic information.

Abstract

Although it is widely accepted that the regulation of the chromatin landscape is pivotal to conveying the epigenetic program, it is still unclear how a defined chromatin domain is reproduced following DNA replication and transmitted from one cell generation to the next. Here, we review the multiple mechanisms that potentially affect the inheritance of epigenetic information in somatic cells. We consider models of how histones might be recycled following replication, and discuss the importance of positive-feedback loops, long-range gene interactions and the complex network of trans-acting factors in the transmission of chromatin states.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Characteristics of a chromatin domain.
Figure 2: The replication fork.
Figure 3: Models of histone deposition during replication.
Figure 4: Propagation of histone 3 lysine 27 trimethylation by polycomb repressive complex 2.
Figure 5: Different phenomena that contribute to propagation of regulatory information.

Similar content being viewed by others

References

  1. Wigler, M., Levy, D. & Perucho, M. The somatic replication of DNA methylation. Cell 24, 33–40 (1981).

    CAS  PubMed  Google Scholar 

  2. Berger, S. L., Kouzarides, T., Shiekhattar, R. & Shilatifard, A. An operational definition of epigenetics. Genes Dev. 23, 781–783 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Trojer, P. & Reinberg, D. Histone lysine demethylases and their impact on epigenetics. Cell 125, 213–217 (2006).

    CAS  PubMed  Google Scholar 

  4. 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).

    CAS  PubMed  Google Scholar 

  5. Kouzarides, T. Chromatin modifications and their function. Cell 128, 693–705 (2007).

    CAS  PubMed  Google Scholar 

  6. Vaquero, A., Loyola, A. & Reinberg, D. The constantly changing face of chromatin. Sci. Aging Knowledge Environ. 2003, re4 (2003).

    PubMed  Google Scholar 

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

    CAS  Google Scholar 

  8. Campos, E. I. & Reinberg, D. Histones: annotating chromatin. Annu. Rev. Genet. 43, 559–599 (2009).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  10. Ekwall, K., Olsson, T., Turner, B. M., Cranston, G. & Allshire, R. C. Transient inhibition of histone deacetylation alters the structural and functional imprint at fission yeast centromeres. Cell 91, 1021–1032 (1997).

    CAS  PubMed  Google Scholar 

  11. Brickner, D. G. et al. H2A.Z-mediated localization of genes at the nuclear periphery confers epigenetic memory of previous transcriptional state. PLoS Biol. 5, e81 (2007).

    PubMed  PubMed Central  Google Scholar 

  12. Kundu, S., Horn, P. J. & Peterson, C. L. SWI/SNF is required for transcriptional memory at the yeast GAL gene cluster. Genes Dev. 21, 997–1004 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Zacharioudakis, I., Gligoris, T. & Tzamarias, D. A yeast catabolic enzyme controls transcriptional memory. Curr. Biol. 17, 2041–2046 (2007).

    CAS  PubMed  Google Scholar 

  14. Ng, H. H., Robert, F., Young, R. A. & Struhl, K. Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol. Cell 11, 709–719 (2003).

    CAS  PubMed  Google Scholar 

  15. Lemieux, K., Larochelle, M. & Gaudreau, L. Variant histone H2A.Z, but not the HMG proteins Nhp6a/b, is essential for the recruitment of Swi/Snf, Mediator, and SAGA to the yeast GAL1 UASG . Biochem. Biophys. Res. Commun. 369, 1103–1107 (2008).

    CAS  PubMed  Google Scholar 

  16. Ansari, A. & Hampsey, M. A role for the CPF 3′-end processing machinery in RNAP II-dependent gene looping. Genes Dev. 19, 2969–2978 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Laine, J. P., Singh, B. N., Krishnamurthy, S. & Hampsey, M. A physiological role for gene loops in yeast. Genes Dev. 23, 2604–2609 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Tan-Wong, S. M., Wijayatilake, H. D. & Proudfoot, N. J. Gene loops function to maintain transcriptional memory through interaction with the nuclear pore complex. Genes Dev. 23, 2610–2624 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Girton, J. R. & Johansen, K. M. Chromatin structure and the regulation of gene expression: the lessons of PEV in Drosophila. Adv. Genet. 61, 1–43 (2008).

    CAS  PubMed  Google Scholar 

  20. Eissenberg, J. C. & Reuter, G. Cellular mechanism for targeting heterochromatin formation in Drosophila. Int. Rev. Cell Mol. Biol. 273, 1–47 (2009).

    CAS  PubMed  Google Scholar 

  21. Schotta, G. et al. Central role of Drosophila SU(VAR)3–9 in histone H3-K9 methylation and heterochromatic gene silencing. EMBO J. 21, 1121–1131 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Ebert, A., Lein, S., Schotta, G. & Reuter, G. Histone modification and the control of heterochromatic gene silencing in Drosophila. Chromosome Res. 14, 377–392 (2006).

    CAS  PubMed  Google Scholar 

  23. Karachentsev, D., Sarma, K., Reinberg, D. & Steward, R. PR-Set7-dependent methylation of histone H4 Lys 20 functions in repression of gene expression and is essential for mitosis. Genes Dev. 19, 431–435 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Brower-Toland, B., Riddle, N. C., Jiang, H., Huisinga, K. L. & Elgin, S. C. Multiple SET methyltransferases are required to maintain normal heterochromatin domains in the genome of Drosophila melanogaster. Genetics 181, 1303–1319 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Bao, X., Deng, H., Johansen, J., Girton, J. & Johansen, K. M. Loss-of-function alleles of the JIL-1 histone H3S10 kinase enhance position-effect variegation at pericentric sites in Drosophila heterochromatin. Genetics 176, 1355–1358 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Sclafani, R. A. & Holzen, T. M. Cell cycle regulation of DNA replication. Annu. Rev. Genet. 41, 237–280 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Machida, Y. J., Hamlin, J. L. & Dutta, A. Right place, right time, and only once: replication initiation in metazoans. Cell 123, 13–24 (2005).

    CAS  PubMed  Google Scholar 

  28. Blow, J. J. & Dutta, A. Preventing re-replication of chromosomal DNA. Nature Rev. Mol. Cell Biol. 6, 476–486 (2005).

    CAS  Google Scholar 

  29. Moldovan, G. L., Pfander, B. & Jentsch, S. PCNA, the maestro of the replication fork. Cell 129, 665–679 (2007).

    CAS  PubMed  Google Scholar 

  30. Tagami, H., Ray-Gallet, D., Almouzni, G. & Nakatani, Y. Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis. Cell 116, 51–61 (2004).

    CAS  PubMed  Google Scholar 

  31. English, C. M., Adkins, M. W., Carson, J. J., Churchill, M. E. & Tyler, J. K. Structural basis for the histone chaperone activity of Asf1. Cell 127, 495–508 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Natsume, R. et al. Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4. Nature 446, 338–341 (2007).

    CAS  PubMed  Google Scholar 

  33. Sobel, R. E., Cook, R. G., Perry, C. A., Annunziato, A. T. & Allis, C. D. Conservation of deposition-related acetylation sites in newly synthesized histones H3 and H4. Proc. Natl Acad. Sci. USA 92, 1237–1241 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Loyola, A., Bonaldi, T., Roche, D., Imhof, A. & Almouzni, G. PTMs on H3 variants before chromatin assembly potentiate their final epigenetic state. Mol. Cell 24, 309–316 (2006).

    CAS  PubMed  Google Scholar 

  35. Li, Q. et al. Acetylation of histone H3 lysine 56 regulates replication-coupled nucleosome assembly. Cell 134, 244–255 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Xie, W. et al. Histone H3 lysine 56 acetylation is linked to the core transcriptional network in human embryonic stem cells. Mol. Cell 33, 417–427 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Das, C., Lucia, M. S., Hansen, K. C. & Tyler, J. K. CBP/p300-mediated acetylation of histone H3 on lysine 56. Nature 459, 113–117 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Tjeertes, J. V., Miller, K. M. & Jackson, S. P. Screen for DNA-damage-responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells. EMBO J. 28, 1878–1889 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Ransom, M., Dennehey, B. K. & Tyler, J. K. Chaperoning histones during DNA replication and repair. Cell 140, 183–195 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Groth, A. et al. Regulation of replication fork progression through histone supply and demand. Science 318, 1928–1931 (2007).

    CAS  PubMed  Google Scholar 

  41. Dodd, I. B., Micheelsen, M. A., Sneppen, K. & Thon, G. Theoretical analysis of epigenetic cell memory by nucleosome modification. Cell 129, 813–822 (2007).

    CAS  PubMed  Google Scholar 

  42. Probst, A. V., Dunleavy, E. & Almouzni, G. Epigenetic inheritance during the cell cycle. Nature Rev. Mol. Cell Biol. 10, 192–206 (2009).

    CAS  Google Scholar 

  43. Shibahara, K. & Stillman, B. Replication-dependent marking of DNA by PCNA facilitates CAF-1-coupled inheritance of chromatin. Cell 96, 575–585 (1999).

    CAS  PubMed  Google Scholar 

  44. Goll, M. G. & Bestor, T. H. Eukaryotic cytosine methyltransferases. Annu. Rev. Biochem. 74, 481–514 (2005).

    CAS  PubMed  Google Scholar 

  45. Li, E., Bestor, T. H. & Jaenisch, R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69, 915–926 (1992).

    CAS  PubMed  Google Scholar 

  46. Egger, G. et al. Identification of DNMT1 (DNA methyltransferase 1) hypomorphs in somatic knockouts suggests an essential role for DNMT1 in cell survival. Proc. Natl Acad. Sci. USA 103, 14080–14085 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Spada, F. et al. DNMT1 but not its interaction with the replication machinery is required for maintenance of DNA methylation in human cells. J. Cell Biol. 176, 565–571 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Chen, T. et al. Complete inactivation of DNMT1 leads to mitotic catastrophe in human cancer cells. Nature Genet. 39, 391–396 (2007).

    CAS  PubMed  Google Scholar 

  49. Jones, P. A. & Liang, G. Rethinking how DNA methylation patterns are maintained. Nature Rev. Genet. 10, 805–811 (2009).

    CAS  PubMed  Google Scholar 

  50. Leonhardt, H., Page, A. W., Weier, H. U. & Bestor, T. H. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell 71, 865–873 (1992).

    CAS  PubMed  Google Scholar 

  51. Chuang, L. S. et al. Human DNA-(cytosine-5) methyltransferase–PCNA complex as a target for p21WAF1. Science 277, 1996–2000 (1997).

    CAS  PubMed  Google Scholar 

  52. Schermelleh, L. et al. Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation. Nucleic Acids Res. 35, 4301–4312 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Sharif, J. et al. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature 450, 908–912 (2007).

    CAS  PubMed  Google Scholar 

  54. Bostick, M. et al. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science 317, 1760–1764 (2007).

    CAS  PubMed  Google Scholar 

  55. Unoki, M., Nishidate, T. & Nakamura, Y. ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain. Oncogene 23, 7601–7610 (2004).

    CAS  PubMed  Google Scholar 

  56. Meissner, A. et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454, 766–770 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Zilberman, D., Coleman-Derr, D., Ballinger, T. & Henikoff, S. Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks. Nature 456, 125–129 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Bernatavichute, Y. V., Zhang, X., Cokus, S., Pellegrini, M. & Jacobsen, S. E. Genome-wide association of histone H3 lysine nine methylation with CHG DNA methylation in Arabidopsis thaliana. PLoS ONE 3, e3156 (2008).

    PubMed  PubMed Central  Google Scholar 

  59. Espada, J. et al. Human DNA methyltransferase 1 is required for maintenance of the histone H3 modification pattern. J. Biol. Chem. 279, 37175–37184 (2004).

    CAS  PubMed  Google Scholar 

  60. Tamaru, H. & Selker, E. U. A histone H3 methyltransferase controls DNA methylation in Neurospora crassa. Nature 414, 277–283 (2001).

    CAS  PubMed  Google Scholar 

  61. Tamaru, H. et al. Trimethylated lysine 9 of histone H3 is a mark for DNA methylation in Neurospora crassa. Nature Genet. 34, 75–79 (2003).

    CAS  PubMed  Google Scholar 

  62. Lehnertz, B. et al. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr. Biol. 13, 1192–1200 (2003).

    CAS  PubMed  Google Scholar 

  63. Dong, K. B. et al. DNA methylation in ES cells requires the lysine methyltransferase G9a but not its catalytic activity. EMBO J. 27, 2691–2701 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Tardat, M., Murr, R., Herceg, Z., Sardet, C. & Julien, E. PR-Set7-dependent lysine methylation ensures genome replication and stability through S phase. J. Cell Biol. 179, 1413–1426 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Jorgensen, S. et al. The histone methyltransferase SET8 is required for S-phase progression. J. Cell Biol. 179, 1337–1345 (2007).

    PubMed  PubMed Central  Google Scholar 

  66. Huen, M. S., Sy, S. M., van Deursen, J. M. & Chen, J. Direct interaction between SET8 and proliferating cell nuclear antigen couples H4-K20 methylation with DNA replication. J. Biol. Chem. 283, 11073–11077 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Rice, J. C. et al. Mitotic-specific methylation of histone H4 Lys 20 follows increased PR-Set7 expression and its localization to mitotic chromosomes. Genes Dev. 16, 2225–2230 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Yin, Y., Yu, V. C., Zhu, G. & Chang, D. C. SET8 plays a role in controlling G1/S transition by blocking lysine acetylation in histone through binding to H4 N-terminal tail. Cell Cycle 7, 1423–1432 (2008).

    CAS  PubMed  Google Scholar 

  69. Oda, H. et al. Monomethylation of histone H4-lysine 20 is involved in chromosome structure and stability and is essential for mouse development. Mol. Cell. Biol. 29, 2278–2295 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  71. Grewal, S. I. & Elgin, S. C. Transcription and RNA interference in the formation of heterochromatin. Nature 447, 399–406 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. James, T. C. & Elgin, S. C. Identification of a nonhistone chromosomal protein associated with heterochromatin in Drosophila melanogaster and its gene. Mol. Cell. Biol. 6, 3862–3872 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 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).

    CAS  PubMed  Google Scholar 

  75. Lachner, M., O'Carroll, D., Rea, S., Mechtler, K. & Jenuwein, T. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 116–120 (2001).

    CAS  PubMed  Google Scholar 

  76. Bannister, A. J. et al. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410, 120–124 (2001).

    CAS  PubMed  Google Scholar 

  77. Stewart, M. D., Li, J. & Wong, J. Relationship between histone H3 lysine 9 methylation, transcription repression, and heterochromatin protein 1 recruitment. Mol. Cell. Biol. 25, 2525–2538 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Sarma, K., Margueron, R., Ivanov, A., Pirrotta, V. & Reinberg, D. Ezh2 requires PHF1 to efficiently catalyze H3 lysine 27 trimethylation in vivo. Mol. Cell. Biol. 28, 2718–2731 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Hansen, K. H. et al. A model for transmission of the H3K27me3 epigenetic mark. Nature Cell Biol. 10, 1291–1300 (2008).

    CAS  PubMed  Google Scholar 

  80. 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 

  81. Vaute, O., Nicolas, E., Vandel, L. & Trouche, D. Functional and physical interaction between the histone methyl transferase Suv39H1 and histone deacetylases. Nucleic Acids Res. 30, 475–481 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Vaquero, A. et al. SIRT1 regulates the histone methyl-transferase SUV39H1 during heterochromatin formation. Nature 450, 440–444 (2007).

    CAS  PubMed  Google Scholar 

  83. Schotta, G. et al. A chromatin-wide transition to H4K20 monomethylation impairs genome integrity and programmed DNA rearrangements in the mouse. Genes Dev. 22, 2048–2061 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  85. Bantignies, F., Grimaud, C., Lavrov, S., Gabut, M. & Cavalli, G. Inheritance of Polycomb-dependent chromosomal interactions in Drosophila. Genes Dev. 17, 2406–2420 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Hekimoglu, B. & Ringrose, L. Non-coding RNAs in polycomb/trithorax regulation. RNA Biol. 6, 129–137 (2009).

    CAS  PubMed  Google Scholar 

  87. Grimaud, C. et al. RNAi components are required for nuclear clustering of Polycomb group response elements. Cell 124, 957–971 (2006).

    CAS  PubMed  Google Scholar 

  88. Lanzuolo, C., Roure, V., Dekker, J., Bantignies, F. & Orlando, V. Polycomb response elements mediate the formation of chromosome higher-order structures in the bithorax complex. Nature Cell Biol. 9, 1167–1174 (2007).

    CAS  PubMed  Google Scholar 

  89. Tiwari, V. K., Cope, L., McGarvey, K. M., Ohm, J. E. & Baylin, S. B. A novel 6C assay uncovers Polycomb-mediated higher order chromatin conformations. Genome Res. 18, 1171–1179 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Buchenau, P., Hodgson, J., Strutt, H. & Arndt-Jovin, D. J. The distribution of polycomb-group proteins during cell division and development in Drosophila embryos: impact on models for silencing. J. Cell Biol. 141, 469–481 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Amaral, P. P. & Mattick, J. S. Noncoding RNA in development. Mamm. Genome 19, 454–492 (2008).

    CAS  PubMed  Google Scholar 

  92. Willingham, A. T. & Gingeras, T. R. TUF love for 'junk' DNA. Cell 125, 1215–1220 (2006).

    CAS  PubMed  Google Scholar 

  93. Moazed, D. Small RNAs in transcriptional gene silencing and genome defence. Nature 457, 413–420 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Volpe, T. A. et al. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297, 1833–1837 (2002).

    CAS  PubMed  Google Scholar 

  95. Pal-Bhadra, M. et al. Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 303, 669–672 (2004).

    CAS  PubMed  Google Scholar 

  96. Henderson, I. R. & Jacobsen, S. E. Epigenetic inheritance in plants. Nature 447, 418–424 (2007).

    CAS  PubMed  Google Scholar 

  97. Wallace, J. A. & Orr-Weaver, T. L. Replication of heterochromatin: insights into mechanisms of epigenetic inheritance. Chromosoma 114, 389–402 (2005).

    CAS  PubMed  Google Scholar 

  98. Kanellopoulou, C. et al. Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev. 19, 489–501 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Murchison, E. P., Partridge, J. F., Tam, O. H., Cheloufi, S. & Hannon, G. J. Characterization of Dicer-deficient murine embryonic stem cells. Proc. Natl Acad. Sci. USA 102, 12135–12140 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Verdel, A., Vavasseur, A., Le Gorrec, M. & Touat-Todeschini, L. Common themes in siRNA-mediated epigenetic silencing pathways. Int. J. Dev. Biol. 53, 245–257 (2009).

    CAS  PubMed  Google Scholar 

  101. Buhler, M., Verdel, A. & Moazed, D. Tethering RITS to a nascent transcript initiates RNAi- and heterochromatin-dependent gene silencing. Cell 125, 873–886 (2006).

    CAS  PubMed  Google Scholar 

  102. Buhler, M., Haas, W., Gygi, S. P. & Moazed, D. RNAi-dependent and -independent RNA turnover mechanisms contribute to heterochromatic gene silencing. Cell 129, 707–721 (2007).

    CAS  PubMed  Google Scholar 

  103. Chen, E. S. et al. Cell cycle control of centromeric repeat transcription and heterochromatin assembly. Nature 451, 734–737 (2008).

    CAS  PubMed  Google Scholar 

  104. Kloc, A., Zaratiegui, M., Nora, E. & Martienssen, R. RNA interference guides histone modification during the S phase of chromosomal replication. Curr. Biol. 18, 490–495 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Reuter, G. et al. Dependence of position-effect variegation in Drosophila on dose of a gene encoding an unusual zinc-finger protein. Nature 344, 219–223 (1990).

    CAS  PubMed  Google Scholar 

  106. Pandey, R. R. et al. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol. Cell 32, 232–246 (2008).

    CAS  PubMed  Google Scholar 

  107. Nagano, T. et al. The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science 322, 1717–1720 (2008).

    CAS  PubMed  Google Scholar 

  108. Zhao, J., Sun, B. K., Erwin, J. A., Song, J. J. & Lee, J. T. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322, 750–756 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Ke, X. S. et al. Genome-wide profiling of histone H3 lysine 4 and lysine 27 trimethylation reveals an epigenetic signature in prostate carcinogenesis. PLoS ONE 4, e4687 (2009).

    PubMed  PubMed Central  Google Scholar 

  110. Cawley, S. et al. Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 116, 499–509 (2004).

    CAS  PubMed  Google Scholar 

  111. Ptashne, M. On the use of the word 'epigenetic'. Curr. Biol. 17, R233–R236 (2007).

    CAS  PubMed  Google Scholar 

  112. Wernig, M. et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448, 318–324 (2007).

    CAS  PubMed  Google Scholar 

  113. Chow, J. & Heard, E. X inactivation and the complexities of silencing a sex chromosome. Curr. Opin. Cell Biol. 21, 359–366 (2009).

    CAS  PubMed  Google Scholar 

  114. Gelbart, M. E. & Kuroda, M. I. Drosophila dosage compensation: a complex voyage to the X chromosome. Development 136, 1399–1410 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank D. Beck, R. Bonasio and E. Campos for their critical reading of the manuscript. We are grateful to L. Vales and J. Hurwitz for critical reading of this manuscript and active discussions. We apologize to authors whose studies could not be cited due to space limitations. Work in the laboratory of D.R. is funded by the US National Institutes of Health (grants RO1GM064844 and 4R37GM037120) and the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Danny Reinberg.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

FlyBase

Fab7

FURTHER INFORMATION

Authors' homepage

Glossary

Histone variants

Structurally distinct, non-typical versions of histone proteins. They are encoded by independent genes and are often subject to regulation that is distinct from that of the canonical histones.

Heterochromatin

The portion of the genome that stays highly condensed throughout the cell cycle. It contains lot of repetitive sequences, is gene-poor overall and is enriched for histone marks, such as histone 3 lysine 9 trimethylation (H3K9me3) and H4K20me3.

Euchromatin

In contrast to heterochromatin, euchromatin is decondensed and is enriched in active genes and histone marks, such as histone 3 lysine 4 trimethylation or histone 3 acetylation, that are associated with active transcription.

Regulon

A group of transcriptional units or operons that are coordinately controlled by a regulator.

Chromatin remodelling

An ATP-dependent enzymatic process that alters histone–DNA interactions or regulates the position of nucleosomes. Chromatin remodelling can also be ATP-independent in the case of the facilitates chromatin transcription (FACT) complex.

Nuclear periphery

The area at the edge of the nucleus. It is normally associated with gene silencing.

Heterokaryon

A cell with two nuclei that share the same cytoplasm.

RNA interference

A cellular mechanism involved in gene silencing and 'protection' from retroviral and transposable element invasion. It is regulated by proteins such as Dicer and Argonaute, which are responsible for the production of small interfering RNAs that target mRNAs for cleavage and that localize silencing factors to heterochromatic regions.

Mini-chromosome maintenance complex

An oligomeric complex that is suggested to be the helicase involved in replication.

Histone chaperone

A protein that binds and escorts histones. Chaperones contribute to histone deposition into chromatin in an ATP-independent manner.

Chromosome conformation capture

A technique used to study the long-distance interactions between genomic regions. These interactions can be used to study the three-dimensional architecture of chromosomes in a cell nucleus.

Small nuclear RNAs

RNAs that are involved in precursor mRNA processing.

Dicer

Dicer proteins are a highly conserved family of RNase III enzymes that mediate dsRNA cleavage. This produces the small RNAs that direct targeted silencing in RNA interference pathways.

Chromatin readers

Protein domains that show high binding affinity for histone post-translational modifications and function in downstream effects.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Margueron, R., Reinberg, D. Chromatin structure and the inheritance of epigenetic information. Nat Rev Genet 11, 285–296 (2010). https://doi.org/10.1038/nrg2752

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg2752

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