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:

Epigenetic inheritance during the cell cycle

Nature Reviews Molecular Cell Biology volume 10, pages 192–206 (2009)Cite this article

Key Points

  • Epigenetic inheritance concerns the mechanisms that ensure transmission of epigenetic marks from mother to daughter cell. Chromatin modifications and nuclear organization are candidates for epigenetic marks — whether they fulfil the criterion of heritability and what mechanisms ensure their propagation is an area of intensive research.

  • The passage of the replication fork challenges genetic and epigenetic information. Depending on the nature of the epigenetic mark, its inheritance can be ensured in a replication-coupled manner or in a timely manner that is separated from the disruptive event.

  • DNA methylation is inherited at the replication fork in a semi-conservative manner. The redistribution of parental histones, together with their parental modifications at the fork, affects the transmission of information. Histone chaperones have an important role in controlling histone dynamics at the fork. The maintenance of DNA methylation and histone modifications is interconnected at the replication fork.

  • The centromere-specific histone H3 variant CenH3 (CENP-A in humans) is inherited in a replication-uncoupled manner — new CENP-A is deposited in late telophase–G1 phase, highlighting a new window of inheritance during the cell cycle.

  • Restoration of pericentric heterochromatin after passage of the replication fork involves an RNA interference-dependent mechanism in fission yeast, whereas for mammals evidence suggests that the DNA methylation maintenance machinery, chromatin assembly factors and histone modifiers operate in a concerted manner to ensure heterochromatin maintenance.

  • Reprogramming during development highlights the reversibility of epigenetic states.

Abstract

Studies that concern the mechanism of DNA replication have provided a major framework for understanding genetic transmission through multiple cell cycles. Recent work has begun to gain insight into possible means to ensure the stable transmission of information beyond just DNA, and has led to the concept of epigenetic inheritance. Considering chromatin-based information, key candidates have arisen as epigenetic marks, including DNA and histone modifications, histone variants, non-histone chromatin proteins, nuclear RNA as well as higher-order chromatin organization. Understanding the dynamics and stability of these marks through the cell cycle is crucial in maintaining a given chromatin state.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Asymmetric DNA replication and coupling of inheritance of DNA and histone marks.
Figure 2: Nucleosome dynamics and mixing of parental and new H3–H4 dimers.
Figure 3: Fate of old and new H3–H4 dimers and their marks at the fork.
Figure 4: Inheritance of histone H3 variants outside of S phase.
Figure 5: Maintaining pericentric heterochromatin in fission yeast and mouse.
Figure 6: Reprogramming during development and the fate of epigenetic marks.

Similar content being viewed by others

References

  1. Riggs, A. D., Martiennssen, R. A. & Russo, V. E. A. in Epigenetic Mechanisms of Gene Regulation 1–4 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1996).

    Google Scholar 

  2. Turner, B. M. Cellular memory and the histone code. Cell 111, 285–291 (2002).

    Article  CAS  PubMed  Google Scholar 

  3. Haig, D. The (dual) origin of epigenetics. Cold Spring Harb. Symp. Quant. Biol. 69, 67–70 (2004).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Bird, A. Perceptions of epigenetics. Nature 447, 396–398 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Ledford, H. Language: disputed definitions. Nature 455, 1023–1028 (2008).

    Article  PubMed  CAS  Google Scholar 

  7. Waddington, C. H. The epigenotype. Endeavour 1 18–20 (1942).

    Google Scholar 

  8. Holliday, R. The inheritance of epigenetic defects. Science 238, 163–170 (1987).

    Article  CAS  PubMed  Google Scholar 

  9. Henikoff, S., Ahmad, K. & Malik, H. S. The centromere paradox: stable inheritance with rapidly evolving DNA. Science 293, 1098–1102 (2001).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  11. Loyola, A. & Almouzni, G. Marking histone H3 variants: how, when and why? Trends Biochem. Sci. 32, 425–433 (2007).

    Article  CAS  PubMed  Google Scholar 

  12. Corpet, A. & Almouzni, G. Making copies of chromatin: the challenge of nucleosomal organization and epigenetic information. Trends Cell Biol. 19, 29–41 (2008).

    Article  PubMed  CAS  Google Scholar 

  13. Groth, A., Rocha, W., Verreault, A. & Almouzni, G. Chromatin challenges during DNA replication and repair. Cell 128, 721–733 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Watson, J. D. & Crick, F. H. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature 171, 737–738 (1953).

    Article  CAS  PubMed  Google Scholar 

  15. DePamphilis, M. L. (ed.) DNA Replication and Human Disease (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2006).

    Google Scholar 

  16. Kunkel, T. A. & Burgers, P. M. Dividing the workload at a eukaryotic replication fork. Trends Cell Biol. 18, 521–527 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  18. Alberts, B. Molecular Biology of the Cell (Garland Science Publishing, London, 2007).

    Book  Google Scholar 

  19. Zhang, Z., Shibahara, K. & Stillman, B. PCNA connects DNA replication to epigenetic inheritance in yeast. Nature 408, 221–225 (2000).

    Article  CAS  PubMed  Google Scholar 

  20. Henderson, D. S., Banga, S. S., Grigliatti, T. A. & Boyd, J. B. Mutagen sensitivity and suppression of position-effect variegation result from mutations in mus209, the Drosophila gene encoding PCNA. EMBO J. 13, 1450–1459 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  22. Moggs, J. G. et al. A CAF-1–PCNA-mediated chromatin assembly pathway triggered by sensing DNA damage. Mol. Cell. Biol. 20, 1206–1218 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Groth, A. et al. Regulation of replication fork progression through histone supply and demand. Science 318, 1928–1931 (2007). Shows that the histone H3 chaperone ASF1 exists in a complex with the putative replicative helicase and suggests that ASF1 handles both parental and new histones at the replication fork.

    Article  CAS  PubMed  Google Scholar 

  24. Bestor, T. H. & Ingram, V. M. Two DNA methyltransferases from murine erythroleukemia cells: purification, sequence specificity, and mode of interaction with DNA. Proc. Natl Acad. Sci. USA 80, 5559–5563 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hermann, A., Goyal, R. & Jeltsch, A. The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites. J. Biol. Chem. 279, 48350–48359 (2004).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  27. Pradhan, S., Bacolla, A., Wells, R. D. & Roberts, R. J. Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation. J. Biol. Chem. 274, 33002–33010 (1999).

    Article  CAS  PubMed  Google Scholar 

  28. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Woo, H. R., Pontes, O., Pikaard, C. S. & Richards, E. J. VIM1, a methylcytosine-binding protein required for centromeric heterochromatinization. Genes Dev. 21, 267–277 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 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).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  33. Bostick, M. et al. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science 317, 1760–1764 (2007). The work reported in references 30, 32 and 33 identified the SRA-domain-containing protein NP95 and its homologue in A. thaliana as essential factors that bind to hemimethylated DNA and are required for faithful DNA methylation inheritance.

    Article  CAS  PubMed  Google Scholar 

  34. Arita, K., Ariyoshi, M., Tochio, H., Nakamura, Y. & Shirakawa, M. Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism. Nature 455, 818–821 (2008).

    Article  CAS  PubMed  Google Scholar 

  35. Avvakumov, G. V. et al. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature 455, 822–825 (2008).

    Article  CAS  PubMed  Google Scholar 

  36. Hashimoto, H. et al. The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix. Nature 455, 826–829 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  38. Jeddeloh, J. A., Stokes, T. L. & Richards, E. J. Maintenance of genomic methylation requires a SWI2/SNF2-like protein. Nature Genet. 22, 94–97 (1999).

    Article  CAS  PubMed  Google Scholar 

  39. Brzeski, J. & Jerzmanowski, A. Deficient in DNA methylation 1 (DDM1) defines a novel family of chromatin-remodeling factors. J. Biol. Chem. 278, 823–828 (2003).

    Article  CAS  PubMed  Google Scholar 

  40. Dennis, K., Fan, T., Geiman, T., Yan, Q. & Muegge, K. Lsh, a member of the SNF2 family, is required for genome-wide methylation. Genes Dev. 15, 2940–2944 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhang, F., Pomerantz, J. H., Sen, G., Palermo, A. T. & Blau, H. M. Active tissue-specific DNA demethylation conferred by somatic cell nuclei in stable heterokaryons. Proc. Natl Acad. Sci. USA 104, 4395–4400 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Metivier, R. et al. Cyclical DNA methylation of a transcriptionally active promoter. Nature 452, 45–50 (2008).

    Article  CAS  PubMed  Google Scholar 

  43. Kangaspeska, S. et al. Transient cyclical methylation of promoter DNA. Nature 452, 112–115 (2008).

    Article  CAS  PubMed  Google Scholar 

  44. Gruenbaum, Y., Cedar, H. & Razin, A. Substrate and sequence specificity of a eukaryotic DNA methylase. Nature 295, 620–622 (1982).

    Article  CAS  PubMed  Google Scholar 

  45. Kimura, H. & Cook, P. R. Kinetics of core histones in living human cells: little exchange of H3 and H4 and some rapid exchange of H2B. J. Cell Biol. 153, 1341–1353 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Jackson, V. & Chalkley, R. A reevaluation of new histone deposition on replicating chromatin. J. Biol. Chem. 256, 5095–5103 (1981).

    Article  CAS  PubMed  Google Scholar 

  47. Polo, S. E. & Almouzni, G. Chromatin assembly: a basic recipe with various flavours. Curr. Opin. Genet. Dev. 16, 104–111 (2006).

    Article  CAS  PubMed  Google Scholar 

  48. De Koning, L., Corpet, A., Haber, J. E. & Almouzni, G. Histone chaperones: an escort network regulating histone traffic. Nature Struct. Mol. Biol. 14, 997–1007 (2007).

    Article  CAS  Google Scholar 

  49. Stillman, B. Chromatin assembly during SV40 DNA replication in vitro. Cell 45, 555–565 (1986). The first report of chromatin assembly coupled in vitro to DNA replication.

    Article  CAS  PubMed  Google Scholar 

  50. Smith, S. & Stillman, B. Purification and characterization of CAF-I, a human cell factor required for chromatin assembly during DNA replication in vitro. Cell 58, 15–25 (1989).

    Article  CAS  PubMed  Google Scholar 

  51. Gaillard, P. H. et al. Chromatin assembly coupled to DNA repair: a new role for chromatin assembly factor I. Cell 86, 887–896 (1996).

    Article  CAS  PubMed  Google Scholar 

  52. Polo, S. E., Roche, D. & Almouzni, G. New histone incorporation marks sites of UV repair in human cells. Cell 127, 481–493 (2006).

    Article  CAS  PubMed  Google Scholar 

  53. Mello, J. A. et al. Human Asf1 and CAF-1 interact and synergize in a repair-coupled nucleosome assembly pathway. EMBO Rep. 3, 329–334 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. 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).

    Article  CAS  PubMed  Google Scholar 

  56. Masumoto, H., Hawke, D., Kobayashi, R. & Verreault, A. A role for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA damage response. Nature 436, 294–298 (2005).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Garcia, B. A. et al. Organismal differences in post-translational modifications in histones H3 and H4. J. Biol. Chem. 282, 7641–7655 (2007).

    Article  CAS  PubMed  Google Scholar 

  59. 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). Shows that the histone variants H3.1 and H3.3 are assembled into chromatin by distinct histone chaperones and suggests that H3 and H4 are deposited as dimers.

    Article  CAS  PubMed  Google Scholar 

  60. Baxevanis, A. D., Godfrey, J. E. & Moudrianakis, E. N. Associative behavior of the histone (H3-H4)2 tetramer: dependence on ionic environment. Biochemistry 30, 8817–8823 (1991).

    Article  CAS  PubMed  Google Scholar 

  61. Verreault, A., Kaufman, P. D., Kobayashi, R. & Stillman, B. Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4. Cell 87, 95–104 (1996).

    Article  CAS  PubMed  Google Scholar 

  62. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  64. Song, J. J., Garlick, J. D. & Kingston, R. E. Structural basis of histone H4 recognition by p55. Genes Dev. 22, 1313–1318 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Murzina, N. V. et al. Structural basis for the recognition of histone H4 by the histone-chaperone RbAp46. Structure 16, 1077–1085 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. 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. Nature Struct. Mol. Biol. 14, 1025–1040 (2007).

    Article  CAS  Google Scholar 

  67. Rea, S. et al. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406, 593–599 (2000).

    Article  CAS  PubMed  Google Scholar 

  68. Aagaard, L. et al. Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3–9 encode centromere-associated proteins which complex with the heterochromatin component M31. EMBO J. 18, 1923–1938 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  70. 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). References 69 and 70 show that HP1 (Swi6 in fission yeast) binds to methylated H3K9 through its chromodomain and suggest that a self-perpetuating loop contributes to HP1 maintenance.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  72. Leffak, I. M., Grainger, R. & Weintraub, H. Conservative assembly and segregation of nucleosomal histones. Cell 12, 837–845 (1977).

    Article  CAS  PubMed  Google Scholar 

  73. Milutinovic, S., Zhuang, Q. & Szyf, M. Proliferating cell nuclear antigen associates with histone deacetylase activity, integrating DNA replication and chromatin modification. J. Biol. Chem. 277, 20974–20978 (2002).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Poot, R. A. et al. The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci. Nature Cell Biol. 6, 1236–1244 (2004).

    Article  CAS  PubMed  Google Scholar 

  77. Sporbert, A., Gahl, A., Ankerhold, R., Leonhardt, H. & Cardoso, M. C. DNA polymerase clamp shows little turnover at established replication sites but sequential de novo assembly at adjacent origin clusters. Mol. Cell 10, 1355–1365 (2002).

    Article  CAS  PubMed  Google Scholar 

  78. Taddei, A., Roche, D., Sibarita, J. B., Turner, B. M. & Almouzni, G. Duplication and maintenance of heterochromatin domains. J. Cell Biol. 147, 1153–1166 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Sarraf, S. A. & Stancheva, I. Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly. Mol. Cell 15, 595–605 (2004).

    Article  CAS  PubMed  Google Scholar 

  80. Reese, B. E., Bachman, K. E., Baylin, S. B. & Rountree, M. R. The methyl-CpG binding protein MBD1 interacts with the p150 subunit of chromatin assembly factor 1. Mol. Cell. Biol. 23, 3226–3236 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Fuks, F., Burgers, W. A., Brehm, A., Hughes-Davies, L. & Kouzarides, T. DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nature Genet. 24, 88–91 (2000).

    Article  CAS  PubMed  Google Scholar 

  82. Rountree, M. R., Bachman, K. E. & Baylin, S. B. DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nature Genet. 25, 269–277 (2000).

    Article  CAS  PubMed  Google Scholar 

  83. Esteve, P. O. et al. Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication. Genes Dev. 20, 3089–3103 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Citterio, E. et al. Np95 is a histone-binding protein endowed with ubiquitin ligase activity. Mol. Cell. Biol. 24, 2526–2535 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Karagianni, P., Amazit, L., Qin, J. & Wong, J. ICBP90, a novel methyl K9 H3 binding protein linking protein ubiquitination with heterochromatin formation. Mol. Cell. Biol. 28, 705–717 (2008).

    Article  CAS  PubMed  Google Scholar 

  86. Ng, R. K. & Gurdon, J. B. Epigenetic memory of an active gene state depends on histone H3.3 incorporation into chromatin in the absence of transcription. Nature Cell Biol. 10, 102–109 (2008).

    Article  CAS  PubMed  Google Scholar 

  87. Zweidler, A. in Histone Genes: Structure, Organization and Regulation (eds Stein, G. S. et al.) 339–371 (Wiley, New York, 1984).

    Google Scholar 

  88. Henikoff, S., Furuyama, T. & Ahmad, K. Histone variants, nucleosome assembly and epigenetic inheritance. Trends Genet. 20, 320–326 (2004).

    Article  CAS  PubMed  Google Scholar 

  89. Ahmad, K. & Henikoff, S. The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. Mol. Cell 9, 1191–1200 (2002).

    Article  CAS  PubMed  Google Scholar 

  90. McKittrick, E., Gafken, P. R., Ahmad, K. & Henikoff, S. Histone H3.3 is enriched in covalent modifications associated with active chromatin. Proc. Natl Acad. Sci. USA 101, 1525–1530 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Jin, C. & Felsenfeld, G. Nucleosome stability mediated by histone variants H3.3 and H2A.Z. Genes Dev. 21, 1519–29 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Henikoff, S. Nucleosome destabilization in the epigenetic regulation of gene expression. Nature Rev. Genet. 9, 15–26 (2008).

    Article  CAS  PubMed  Google Scholar 

  93. Ray-Gallet, D. et al. HIRA is critical for a nucleosome assembly pathway independent of DNA synthesis. Mol. Cell 9, 1091–1100 (2002).

    Article  CAS  PubMed  Google Scholar 

  94. Cleveland, D. W., Mao, Y. & Sullivan, K. F. Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling. Cell 112, 407–421 (2003).

    Article  CAS  PubMed  Google Scholar 

  95. Allshire, R. C. & Karpen, G. H. Epigenetic regulation of centromeric chromatin: old dogs, new tricks? Nature Rev. Genet. 9, 923–937 (2008).

    Article  CAS  PubMed  Google Scholar 

  96. Hemmerich, P. et al. Dynamics of inner kinetochore assembly and maintenance in living cells. J. Cell Biol. 180, 1101–1114 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Shelby, R. D., Monier, K. & Sullivan, K. F. Chromatin assembly at kinetochores is uncoupled from DNA replication. J. Cell Biol. 151, 1113–1118 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Jansen, L. E., Black, B. E., Foltz, D. R. & Cleveland, D. W. Propagation of centromeric chromatin requires exit from mitosis. J. Cell Biol. 176, 795–805 (2007). This elegant study, which uses SNAP-tag technology, shows that new CENP-A is deposited in a discrete time window at late telophase–G1 phase.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Sullivan, K. F. A solid foundation: functional specialization of centromeric chromatin. Curr. Opin. Genet. Dev. 11, 182–188 (2001).

    Article  CAS  PubMed  Google Scholar 

  100. Mizuguchi, G., Xiao, H., Wisniewski, J., Smith, M. M. & Wu, C. Nonhistone Scm3 and histones CenH3–H4 assemble the core of centromere-specific nucleosomes. Cell 129, 1153–1164 (2007).

    Article  CAS  PubMed  Google Scholar 

  101. Dalal, Y., Wang, H., Lindsay, S. & Henikoff, S. Tetrameric structure of centromeric nucleosomes in interphase Drosophila cells. PLoS Biol. 5, e218 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Conde e Silva, N. et al. CENP-A-containing nucleosomes: easier disassembly versus exclusive centromeric localization. J. Mol. Biol. 370, 555–573 (2007).

    Article  CAS  PubMed  Google Scholar 

  103. Bernard, P. et al. Requirement of heterochromatin for cohesion at centromeres. Science 294, 2539–2542 (2001).

    Article  CAS  PubMed  Google Scholar 

  104. Nonaka, N. et al. Recruitment of cohesin to heterochromatic regions by Swi6/HP1 in fission yeast. Nature Cell Biol. 4, 89–93 (2002).

    Article  CAS  PubMed  Google Scholar 

  105. Yamada, T., Fischle, W., Sugiyama, T., Allis, C. D. & Grewal, S. I. The nucleation and maintenance of heterochromatin by a histone deacetylase in fission yeast. Mol. Cell 20, 173–185 (2005).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  107. 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). References 106 and 107 show that transcription and processing of centromeric repeats occurs in a discrete window during the cell cycle.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Kim, S. M., Dubey, D. D. & Huberman, J. A. Early-replicating heterochromatin. Genes Dev. 17, 330–335 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Volpe, T. A. et al. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297, 1833–1837 (2002). The first observation to link the RNAi pathway to heterochromatin maintenance in fission yeast.

    Article  CAS  PubMed  Google Scholar 

  110. Verdel, A. et al. RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303, 672–676 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Sugiyama, T., Cam, H., Verdel, A., Moazed, D. & Grewal, S.I. RNA-dependent RNA polymerase is an essential component of a self-enforcing loop coupling heterochromatin assembly to siRNA production. Proc. Natl Acad. Sci. USA 102, 152–157 (2005).

    Article  CAS  PubMed  Google Scholar 

  112. Shankaranarayana, G. D., Motamedi, M. R., Moazed, D. & Grewal, S. I. Sir2 regulates histone H3 lysine 9 methylation and heterochromatin assembly in fission yeast. Curr. Biol. 13, 1240–1246 (2003).

    Article  CAS  PubMed  Google Scholar 

  113. Grewal, S. I. & Jia, S. Heterochromatin revisited. Nature Rev. Genet. 8, 35–46 (2007).

    Article  CAS  PubMed  Google Scholar 

  114. Fukagawa, T. et al. Dicer is essential for formation of the heterochromatin structure in vertebrate cells. Nature Cell Biol. 6, 784–791 (2004).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Rudert, F., Bronner, S., Garnier, J. M. & Dolle, P. Transcripts from opposite strands of gamma satellite DNA are differentially expressed during mouse development. Mamm. Genome 6, 76–83 (1995).

    Article  CAS  PubMed  Google Scholar 

  118. 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).

    Article  CAS  PubMed  Google Scholar 

  119. Lu, J. & Gilbert, D. M. Cell cycle regulated transcription of heterochromatin in mammals vs. fission yeast: functional conservation or coincidence? Cell Cycle 7, 1907–1910 (2008).

    Article  CAS  PubMed  Google Scholar 

  120. Muchardt, C. et al. Coordinated methyl and RNA binding is required for heterochromatin localization of mammalian HP1α. EMBO Rep. 3, 975–981 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Maison, C. et al. Higher-order structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA component. Nature Genet. 30, 329–334 (2002).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  123. Hirota, T., Lipp, J. J., Toh, B. H. & Peters, J. M. Histone H3 serine 10 phosphorylation by Aurora B causes HP1 dissociation from heterochromatin. Nature 438, 1176–1180 (2005).

    Article  CAS  PubMed  Google Scholar 

  124. Guenatri, M., Bailly, D., Maison, C. & Almouzni, G. Mouse centric and pericentric satellite repeats form distinct functional heterochromatin. J. Cell Biol. 166, 493–505 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Wu, R., Singh, P. B. & Gilbert, D. M. Uncoupling global and fine-tuning replication timing determinants for mouse pericentric heterochromatin. J. Cell Biol. 174, 185–194 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Lu, J. & Gilbert, D. M. Proliferation-dependent and cell cycle regulated transcription of mouse pericentric heterochromatin. J. Cell Biol. 179, 411–421 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. 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).

    Article  CAS  PubMed  Google Scholar 

  128. Quivy, J. P. et al. A CAF-1 dependent pool of HP1 during heterochromatin duplication. EMBO J. 23, 3516–3526 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Murzina, N., Verreault, A., Laue, E. & Stillman, B. Heterochromatin dynamics in mouse cells: interaction between chromatin assembly factor 1 and HP1 proteins. Mol. Cell 4, 529–540 (1999).

    Article  CAS  PubMed  Google Scholar 

  130. Quivy, J. P., Gerard, A., Cook, A. J., Roche, D. & Almouzni, G. The HP1–p150/CAF-1 interaction is required for pericentric heterochromatin replication and S-phase progression in mouse cells. Nature Struct. Mol. Biol. 15, 972–979 (2008).

    Article  CAS  Google Scholar 

  131. Houlard, M. et al. CAF-1 is essential for heterochromatin organization in pluripotent embryonic cells. PLoS Genet. 2, e181 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Taddei, A., Maison, C., Roche, D. & Almouzni, G. Reversible disruption of pericentric heterochromatin and centromere function by inhibiting deacetylases. Nature Cell Biol. 3, 114–120 (2001).

    Article  CAS  PubMed  Google Scholar 

  133. Funabiki, H., Hagan, I., Uzawa, S. & Yanagida, M. Cell cycle-dependent specific positioning and clustering of centromeres and telomeres in fission yeast. J. Cell Biol. 121, 961–976 (1993).

    Article  CAS  PubMed  Google Scholar 

  134. Heitz, E. Das heterochromatin der moose. Jahrbuch Wiss Botanik, 762–818 (1928) (in German).

  135. Brown, S. W. Heterochromatin. Science 151, 417–425 (1966).

    Article  CAS  PubMed  Google Scholar 

  136. Probst, A. V., Santos, F., Reik, W., Almouzni, G. & Dean, W. Structural differences in centromeric heterochromatin are spatially reconciled on fertilisation in the mouse zygote. Chromosoma 116, 403–415 (2007).

    Article  PubMed  Google Scholar 

  137. Probst, A. V. & Almouzni, G. Pericentric heterochromatin: dynamic organization during early development in mammals. Differentiation 76, 15–23 (2008).

    Article  CAS  PubMed  Google Scholar 

  138. Mayer, W., Niveleau, A., Walter, J., Fundele, R. & Haaf, T. Demethylation of the zygotic paternal genome. Nature 403, 501–502 (2000). The first illustration of selective DNA demethylation of the paternal genome.

    Article  CAS  PubMed  Google Scholar 

  139. Santos, F., Hendrich, B., Reik, W. & Dean, W. Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev. Biol. 241, 172–182 (2002).

    Article  CAS  PubMed  Google Scholar 

  140. Santos, F., Peters, A. H., Otte, A. P., Reik, W. & Dean, W. Dynamic chromatin modifications characterise the first cell cycle in mouse embryos. Dev. Biol. 280, 225–236 (2005).

    Article  CAS  PubMed  Google Scholar 

  141. Martin, C. et al. Genome restructuring in mouse embryos during reprogramming and early development. Dev. Biol. 292, 317–332 (2006).

    Article  CAS  PubMed  Google Scholar 

  142. Farthing, C. R. et al. Global mapping of DNA methylation in mouse promoters reveals epigenetic reprogramming of pluripotency genes. PLoS Genet. 4, e1000116 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  143. Hajkova, P. et al. Chromatin dynamics during epigenetic reprogramming in the mouse germ line. Nature 452, 877–881 (2008).

    Article  CAS  PubMed  Google Scholar 

  144. Lee, J. et al. Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells. Development 129, 1807–1817 (2002).

    Article  CAS  PubMed  Google Scholar 

  145. Hajkova, P. et al. Epigenetic reprogramming in mouse primordial germ cells. Mech. Dev. 117, 15–23 (2002).

    Article  CAS  PubMed  Google Scholar 

  146. Bannister, A. J. & Kouzarides, T. Reversing histone methylation. Nature 436, 1103–1106 (2005).

    Article  CAS  PubMed  Google Scholar 

  147. Rougier, N. et al. Chromosome methylation patterns during mammalian preimplantation development. Genes Dev. 12, 2108–2113 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Howell, C. Y. et al. Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell 104, 829–838 (2001).

    Article  CAS  PubMed  Google Scholar 

  149. Morgan, H. D., Santos, F., Green, K., Dean, W. & Reik, W. Epigenetic reprogramming in mammals. Hum. Mol. Genet. 14, R47–R58 (2005).

    Article  CAS  PubMed  Google Scholar 

  150. Reik, W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447, 425–432 (2007).

    Article  CAS  PubMed  Google Scholar 

  151. Choi, Y. et al. DEMETER, a DNA glycosylase domain protein, is required for endosperm gene imprinting and seed viability in Arabidopsis. Cell 110, 33–42 (2002).

    Article  CAS  PubMed  Google Scholar 

  152. Gong, Z. et al. ROS1, a repressor of transcriptional gene silencing in Arabidopsis, encodes a DNA glycosylase/lyase. Cell 111, 803–814 (2002).

    Article  CAS  PubMed  Google Scholar 

  153. Barreto, G. et al. Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature 445, 671–675 (2007).

    Article  CAS  PubMed  Google Scholar 

  154. Jin, S. G., Guo, C. & Pfeifer, G. P. GADD45A does not promote DNA demethylation. PLoS Genet. 4, e1000013 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  155. Ooi, S. K. & Bestor, T. H. The colorful history of active DNA demethylation. Cell 133, 1145–1148 (2008).

    Article  CAS  PubMed  Google Scholar 

  156. van der Heijden, G. W. et al. Transmission of modified nucleosomes from the mouse male germline to the zygote and subsequent remodeling of paternal chromatin. Dev. Biol. 298, 458–469 (2006).

    Article  CAS  PubMed  Google Scholar 

  157. Hochedlinger, K. et al. Reprogramming of a melanoma genome by nuclear transplantation. Genes Dev. 18, 1875–1885 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006). Demonstrates that somatic cells can be reprogrammed to an embryonic cell fate by forced expression of embryonic transcription factors.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  160. Tada, M., Takahama, Y., Abe, K., Nakatsuji, N. & Tada, T. Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr. Biol. 11, 1553–1558 (2001).

    Article  CAS  PubMed  Google Scholar 

  161. Roemer, I., Reik, W., Dean, W. & Klose, J. Epigenetic inheritance in the mouse. Curr. Biol. 7, 277–280 (1997).

    Article  CAS  PubMed  Google Scholar 

  162. Morgan, H. D., Sutherland, H. G., Martin, D. I. & Whitelaw, E. Epigenetic inheritance at the agouti locus in the mouse. Nature Genet. 23, 314–318 (1999).

    Article  CAS  PubMed  Google Scholar 

  163. Rakyan, V. K. et al. Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc. Natl Acad. Sci. USA 100, 2538–2543 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Buiting, K. et al. Epimutations in Prader–Willi and Angelman syndromes: a molecular study of 136 patients with an imprinting defect. Am. J. Hum. Genet. 72, 571–577 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Blewitt, M. E., Vickaryous, N. K., Paldi, A., Koseki, H. & Whitelaw, E. Dynamic reprogramming of DNA methylation at an epigenetically sensitive allele in mice. PLoS Genet. 2, e49 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Cropley, J. E., Suter, C. M., Beckman, K. B. & Martin, D. I. Germ-line epigenetic modification of the murine Avy allele by nutritional supplementation. Proc. Natl Acad. Sci. USA 103, 17308–17312 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Morgan, D. K. & Whitelaw, E. The case for transgenerational epigenetic inheritance in humans. Mamm. Genome 19, 394–397 (2008).

    Article  PubMed  Google Scholar 

  168. Lolle, S. J., Victor, J. L., Young, J. M. & Pruitt, R. E. Genome-wide non-mendelian inheritance of extra-genomic information in Arabidopsis. Nature 434, 505–509 (2005).

    Article  CAS  PubMed  Google Scholar 

  169. Rassoulzadegan, M. et al. RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature 441, 469–474 (2006).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  171. Lepere, G., Betermier, M., Meyer, E. & Duharcourt, S. Maternal noncoding transcripts antagonize the targeting of DNA elimination by scanRNAs in Paramecium tetraurelia. Genes Dev. 22, 1501–1512 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Lippman, Z. & Martienssen, R. The role of RNA interference in heterochromatic silencing. Nature 431, 364–370 (2004).

    Article  CAS  PubMed  Google Scholar 

  173. McNairn, A. J. & Gilbert, D. M. Epigenomic replication: linking epigenetics to DNA replication. Bioessays 25, 647–656 (2003).

    Article  CAS  PubMed  Google Scholar 

  174. Fox, M. H., Arndt-Jovin, D. J., Jovin, T. M., Baumann, P. H. & Robert-Nicoud, M. Spatial and temporal distribution of DNA replication sites localized by immunofluorescence and confocal microscopy in mouse fibroblasts. J. Cell Sci. 99, 247–253 (1991).

    Article  PubMed  Google Scholar 

  175. O'Keefe, R. T., Henderson, S. C. & Spector, D. L. Dynamic organization of DNA replication in mammalian cell nuclei: spatially and temporally defined replication of chromosome-specific alpha-satellite DNA sequences. J. Cell Biol. 116, 1095–1110 (1992).

    Article  CAS  PubMed  Google Scholar 

  176. Hiratani, I. et al. Global reorganization of replication domains during embryonic stem cell differentiation. PLoS Biol. 6, e245 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  177. Gilbert, D. M. Replication timing and transcriptional control: beyond cause and effect. Curr. Opin. Cell Biol. 14, 377–383 (2002).

    Article  CAS  PubMed  Google Scholar 

  178. Misteli, T. Beyond the sequence: cellular organization of genome function. Cell 128, 787–800 (2007).

    Article  CAS  PubMed  Google Scholar 

  179. Tatematsu, K. I., Yamazaki, T. & Ishikawa, F. MBD2–MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase. Genes Cells 5, 677–688 (2000).

    Article  CAS  PubMed  Google Scholar 

  180. Bozhenok, L., Wade, P. A. & Varga-Weisz, P. WSTF–ISWI chromatin remodeling complex targets heterochromatic replication foci. EMBO J. 21, 2231–2241 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Maison, C. & Almouzni, G. HP1 and the dynamics of heterochromatin maintenance. Nature Rev. Mol. Cell Biol. 5, 296–304 (2004).

    Article  CAS  Google Scholar 

  182. van der Heijden, G. W. et al. Asymmetry in histone H3 variants and lysine methylation between paternal and maternal chromatin of the early mouse zygote. Mech. Dev. 122, 1008–1022 (2005).

    Article  CAS  PubMed  Google Scholar 

  183. Torres-Padilla, M. E., Bannister, A. J., Hurd, P. J., Kouzarides, T. & Zernicka-Goetz, M. Dynamic distribution of the replacement histone variant H3.3 in the mouse oocyte and preimplantation embryos. Int. J. Dev. Biol. 50, 455–461 (2006).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We apologize for not quoting all of our colleagues for their contributions owing to space limitations. We thank D. Roche for providing images, J. P. Quivy and P. A. Defossez for critical comments to the manuscript. A.V.P. is supported by a European Molecular Biology Organization (EMBO) long-term fellowship. A.V.P., E.D. and G.A. are supported by La Ligue Nationale contre le Cancer (Equipe Labellisée la Ligue), Programme Incitatif Cooperatif (PIC) programmes 'Retinoblastome' and 'Replication, Instabilite chromosomique et cancer', the European Commission Network of Excellence Epigenome, ACI-2007-Cancéropôle IdF 'Breast cancer and Epigenetics' and the Agence Nationale de la Recherche.

Author information

Author notes

  1. Aline V. Probst and Elaine Dunleavy: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Nuclear Dynamics and Genome Plasticity, UMR218 Centre National de la Recherche Scientifique/Institut Curie, 26, rue d'Ulm, Paris Cedex 05, 75231, France

    Aline V. Probst, Elaine Dunleavy & Geneviève Almouzni

Authors
  1. Aline V. Probst
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elaine Dunleavy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Geneviève Almouzni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Geneviève Almouzni.

Related links

Related links

DATABASES

Interpro

RING

SET

FURTHER INFORMATION

Geneviève Almouzni's homepage

Glossary

Epigenetics

This term was coined by Waddington in 1942 to describe how genes of a genotype bring about a phenotype. Current definitions of epigenetics include the study of heritable changes in gene function that occur without alterations to the DNA sequence.

Centromere

A region of a chromosome that is defined by the presence of a centromere-specific histone H3 variant (CenH3) and that functions as a platform for kinetochore assembly during mitosis.

Heterochromatin

A chromatin region that remains condensed throughout the cell cycle and that is characterized by a specific chromatin signature.

Reprogramming

The induced reversal of an epigenetic state, resulting in an altered cellular identity.

Histone chaperone

A factor that associates with histones and stimulates a reaction that involves histone transfer without being part of the final product.

DNA methyltransferase

An enzyme that transfers methyl groups from S-adenosylmethionine to specific adenines or cytosines in DNA.

Histone H3 variant

A replicative histone H3 variant is expressed and incorporated during DNA replication (for example, H3.1 and H3.2), whereas a replacement variant is expressed throughout the cell cycle and is incorporated in a DNA-synthesis-independent manner (for example, H3.3 and the centromere-specific histone H3 variant CenH3).

Histone deacetylase

An enzyme that removes acetyl groups from histones.

Lys methyltransferase

An enzyme that catalyses the addition of a methyl group to specific Lys residues in histones and other non-histone proteins.

Lys acetyltransferase

An enzyme that catalyses the addition of an acetyl group to specific Lys residues in histones and other non-histone proteins.

Heterochromatin protein 1

(HP1). A chromodomain-containing protein that binds to methylated K9 on histone H3 and is associated with heterochromatin in fission yeast (Swi6), mammals (HP1) and Drosophila melanogaster (HP1).

Pericentric heterochromatin

A heterochromatic region adjacent to chromatin containing the centromere-specific histone H3 variant CenH3, and which is considered to be typical constitutive heterochromatin.

Small interfering RNA

A short, non-coding RNA (∼22-nt long) that is processed from longer double-stranded RNA by the RNA interference machinery. Such non-coding RNAs confer target specificity to the silencing complexes in which they reside.

Phospho–methyl switch

The phosphorylation of histone H3S10 during late G2 phase and mitosis interferes with the binding of heterochromatin protein 1 to the adjacent methylated H3K9 residue.

Chromocentre

A cluster of constitutive heterochromatin from different chromosomes that is formed during interphase.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Probst, A., Dunleavy, E. & Almouzni, G. Epigenetic inheritance during the cell cycle. Nat Rev Mol Cell Biol 10, 192–206 (2009). https://doi.org/10.1038/nrm2640

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm2640

This article is cited by

Search

Advanced 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