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:

HP1 and the dynamics of heterochromatin maintenance

Nature Reviews Molecular Cell Biology volume 5, pages 296–305 (2004)Cite this article

Key Points

  • Pericentric heterochromatin is found juxtaposed to the centromere, and is a region of chromatin that remains condensed throughout the cell cycle. Its maintenance is thought to be essential for correct chromosome segregation.

  • At the molecular level, a prominent mark of pericentric heterochromatin is its enrichment in heterochromatin protein-1 (HP1). The multipartite organization of HP1 enables it to bind to numerous nuclear proteins. Among these proteins, those that are potentially involved in the stability of the higher-order structure of pericentric heterochromatin are highlighted. In this way, how HP1 proteins might participate in promoting the self perpetuation of the nuclear domain to which they belong is illustrated.

  • In addition to HP1, epigenetic parameters that are key to the stability of pericentric heterochromatin in mouse are histone-H3 methylated at lysine 9 (H3-K9), hypoacetylated histones, H3-K9 methyltransferase Suv39h and an RNA component. Consistent with this idea, a key aspect in the stability of pericentric heterochromatin is therefore the inter-relationship between these various components. We propose that a local enrichment of HP1 can be achieved by the numerous binding partners that individually have a relatively low affinity.

  • The nature of the interaction of HP1 with its partners within the pericentric heterochromatin domain is highly dynamic, and the properties of HP1 can be integrated into a model for the stable inheritance of the pericentric heterochromatin structure during DNA replication.

  • Finally, exciting recent discoveries implicate RNA in pericentric chromatin maintenance. We compare pericentric heterochromatin in mouse cells and in Schizosaccharomyces pombe and discuss the respective functions of RNA in these regions. An unknown RNA component is required for the maintenance of the mouse pericentric heterochromatin organization, and in S. pombe the RNA-interference machinery is required for the formation of heterochromatin at centromeres.

Abstract

Heterochromatin maintenance is crucial for the clonal inheritance of cell identity, to ensure the proper segregation of chromosomes and the regulation of gene expression. Although it is architecturally stable, heterochromatin has to be flexible to cope with disrupting events such as replication. Recent progress has shed light on the paradoxical properties of heterochromatin in the nucleus, and highlights the roles of heterochromatin protein-1 and, more unexpectedly, RNA molecules in heterochromatin maintenance.

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: Mouse pericentric heterochromatin.
Figure 2: Mouse HP1 domains and interaction partners.
Figure 3: The ins and outs at the replication fork: a model for heterochromatin propagation.

Similar content being viewed by others

References

  1. Flemming, W. Zell substanz, Kern und Zelltheilung, (Vogel, Leipzig, 1882).

    Book  Google Scholar 

  2. Heitz, E. Das heterochromatin der Moose. Jb. Wiss. Bot. 69, 728 (1928).

    Google Scholar 

  3. Sullivan, B. A., Blower, M. D. & Karpen, G. H. Determining centromere identity: cyclical stories and forking paths. Nature Rev. Genet. 2, 584–596 (2001).

    Article  CAS  PubMed  Google Scholar 

  4. Dillon, N. & Festenstein, R. Unravelling heterochromatin: competition between positive and negative factors regulates accessibility. Trends Genet. 18, 252–258 (2002).

    Article  CAS  PubMed  Google Scholar 

  5. Vissel, B. & Choo, K. H. Mouse major (γ) satellite DNA is highly conserved and organized into extremely long tandem arrays: implications for recombination between nonhomologous chromosomes. Genomics 5, 407–414 (1989).

    Article  CAS  PubMed  Google Scholar 

  6. 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 

  7. Peters, A. H. et al. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 107, 323–337 (2001).

    Article  CAS  PubMed  Google Scholar 

  8. 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).

    Article  CAS  PubMed  Google Scholar 

  9. Francastel, C., Walters, M. C., Groudine, M. & Martin, D. I. A functional enhancer suppresses silencing of a transgene and prevents its localization close to centromeric heterochromatin. Cell 99, 259–269 (1999).

    Article  CAS  PubMed  Google Scholar 

  10. Brown, K. E., Baxter, J., Graf, D., Merkenschlager, M. & Fisher, A. G. Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division. Mol. Cell 3, 207–217 (1999).

    Article  CAS  PubMed  Google Scholar 

  11. Henikoff, S. Position-effect variegation after 60 years. Trends Genet. 6, 422–426 (1990).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  13. Jeppesen, P., Mitchell, A., Turner, B. & Perry, P. Antibodies to defined histone epitopes reveal variations in chromatin conformation and underacetylation of centric heterochromatin in human metaphase chromosomes. Chromosoma 101, 322–332 (1992).

    Article  CAS  PubMed  Google Scholar 

  14. 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 

  15. James, T. C. et al. Distribution patterns of HP1, a heterochromatin-associated nonhistone chromosomal protein of Drosophila. Eur. J. Cell Biol. 50, 170–180 (1989).

    CAS  PubMed  Google Scholar 

  16. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Singh, P. B. et al. A sequence motif found in a Drosophila heterochromatin protein is conserved in animals and plants. Nucleic Acids Res. 19, 789–794 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Minc, E., Courvalin, J. C. & Buendia, B. HP1γ associates with euchromatin and heterochromatin in mammalian nuclei and chromosomes. Cytogenet. Cell Genet. 90, 279–284 (2000).

    Article  CAS  PubMed  Google Scholar 

  19. Nielsen, A. L. et al. Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins. Mol. Cell 7, 729–739 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. Gilbert, N. et al. Formation of facultative heterochromatin in the absence of HP1. Embo J. 22, 5540–5550 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jones, D. O., Cowell, I. G. & Singh, P. B. Mammalian chromodomain proteins: their role in genome organisation and expression. Bioessays 22, 124–137 (2000).

    Article  CAS  PubMed  Google Scholar 

  22. Ball, L. J. et al. Structure of the chromatin binding (chromo) domain from mouse modifier protein 1. Embo J. 16, 2473–2481 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Nielsen, P. R. et al. Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9. Nature 416, 103–107 (2002).

    Article  CAS  PubMed  Google Scholar 

  24. Brasher, S. V. et al. The structure of mouse HP1 suggests a unique mode of single peptide recognition by the shadow chromo domain dimer. EMBO J. 19, 1587–1597 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cowieson, N. P., Partridge, J. F., Allshire, R. C. & McLaughlin, P. J. Dimerisation of a chromo shadow domain and distinctions from the chromodomain as revealed by structural analysis. Curr. Biol. 10, 517–525 (2000).

    Article  CAS  PubMed  Google Scholar 

  26. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li, Y., Kirschmann, D. A. & Wallrath, L. L. Does heterochromatin protein 1 always follow code? Proc. Natl Acad. Sci. USA 99, 16462–16469 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 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).

    Article  CAS  PubMed  Google Scholar 

  29. 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 

  30. Strahl, B. D. & Allis, C. D. The language of covalent histone modifications. Nature 403, 41–45 (2000).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  33. 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 

  34. Grewal, S. I. & Moazed, D. Heterochromatin and epigenetic control of gene expression. Science 301, 798–802 (2003).

    Article  CAS  PubMed  Google Scholar 

  35. Akhtar, A., Zink, D. & Becker, P. B. Chromodomains are protein–RNA interaction modules. Nature 407, 405–409 (2000).

    Article  CAS  PubMed  Google Scholar 

  36. 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). This paper shows that a RNA component is required for the maintenance of the mouse pericentric-heterochromatin organization.

    Article  PubMed  Google Scholar 

  37. 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 

  38. Sugimoto, K., Yamada, T., Muro, Y. & Himeno, M. Human homolog of Drosophila heterochromatin-associated protein 1 (HP1) is a DNA-binding protein which possesses a DNA-binding motif with weak similarity to that of human centromere protein C (CENP-C). J. Biochem. (Tokyo) 120, 153–159 (1996).

    Article  CAS  Google Scholar 

  39. Meehan, R. R., Kao, C. F. & Pennings, S. HP1 binding to native chromatin in vitro is determined by the hinge region and not by the chromodomain. Embo J. 22, 3164–3174 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Smothers, J. F. & Henikoff, S. The HP1 chromo shadow domain binds a consensus peptide pentamer. Curr. Biol. 10, 27–30 (2000).

    Article  CAS  PubMed  Google Scholar 

  41. Le Douarin, B. et al. A possible involvement of TIF1α and TIF1β in the epigenetic control of transcription by nuclear receptors. Embo J. 15, 6701–6715 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Fuks, F., Hurd, P. J., Deplus, R. & Kouzarides, T. The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res. 31, 2305–2312 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Okano, M., Bell, D. W., Haber, D. A. & Li, E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247–257 (1999).

    Article  CAS  PubMed  Google Scholar 

  44. Robertson, K. D. DNA methylation and chromatin — unraveling the tangled web. Oncogene 21, 5361–5379 (2002).

    Article  CAS  PubMed  Google Scholar 

  45. 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 

  46. Mello, J. A. & Almouzni, G. The ins and outs of nucleosome assembly. Curr. Opin. Genet. Dev. 11, 136–141 (2001).

    Article  CAS  PubMed  Google Scholar 

  47. 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).

    Article  CAS  PubMed  Google Scholar 

  48. Rice, J. C. et al. Histone methyltransferases direct different degrees of methylation to define distinct chromatin domains. Mol. Cell 12, 1591–1598 (2003).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  50. Jacobs, S. A. & Khorasanizadeh, S. Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail. Science 295, 2080–2083 (2002).

    Article  CAS  PubMed  Google Scholar 

  51. Peters, A. H. et al. Histone H3 lysine 9 methylation is an epigenetic imprint of facultative heterochromatin. Nature Genet. 30, 77–80 (2002).

    Article  CAS  PubMed  Google Scholar 

  52. Chadwick, B. P. & Willard, H. F. Chromatin of the Barr body: histone and non-histone proteins associated with or excluded from the inactive X chromosome. Hum. Mol. Genet. 12, 2167–2178 (2003).

    Article  CAS  PubMed  Google Scholar 

  53. Avner, P. & Heard, E. X-chromosome inactivation: counting, choice and initiation. Nature Rev. Genet. 2, 59–67 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. David, G., Turner, G. M., Yao, Y., Protopopov, A. & DePinho, R. A. mSin3-associated protein, mSds3, is essential for pericentric heterochromatin formation and chromosome segregation in mammalian cells. Genes Dev. 17, 2396–2405 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  56. 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 

  57. Cheutin, T. et al. Maintenance of stable heterochromatin domains by dynamic HP1 binding. Science 299, 721–725 (2003).

    Article  CAS  PubMed  Google Scholar 

  58. Festenstein, R. et al. Modulation of heterochromatin protein 1 dynamics in primary mammalian cells. Science 299, 719–721 (2003). References 57 and 58 demonstrate that the heterochromatin protein HP1 is highly dynamic within stable heterochromatin domains.

    Article  CAS  PubMed  Google Scholar 

  59. Gruss, C., Wu, J., Koller, T. & Sogo, J. M. Disruption of the nucleosomes at the replication fork. Embo J. 12, 4533–4545 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Wolffe, A. P. & Brown, D. D. DNA replication in vitro erases a Xenopus 5S RNA gene transcription complex. Cell 47, 217–227 (1986).

    Article  CAS  PubMed  Google Scholar 

  61. 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 

  62. Collins, N. et al. An ACF1-ISWI chromatin-remodeling complex is required for DNA replication through heterochromatin. Nature Genet. 32, 627–632 (2002).

    Article  CAS  PubMed  Google Scholar 

  63. McDowell, T. L. et al. Localization of a putative transcriptional regulator (ATRX) at pericentromeric heterochromatin and the short arms of acrocentric chromosomes. Proc. Natl Acad. Sci. USA 96, 13983–13988 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Nielsen, A. L. et al. Selective interaction between the chromatin-remodeling factor BRG1 and the heterochromatin-associated protein HP1α. Embo J. 21, 5797–5806 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Sogo, J. M. & Laskey, R. A. in Chromatin Structure and Gene Expression (ed. Elgin, S. C. R.) 49–71 (Oxford Univ. Press, New York, 1995)

    Google Scholar 

  67. Shibahara, K. I. & 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 

  68. 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 

  69. 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 

  70. Vermaak, D., Ahmad, K. & Henikoff, S. Maintenance of chromatin states: an open-and-shut case. Curr. Opin. Cell Biol. 15, 266–274 (2003).

    Article  CAS  PubMed  Google Scholar 

  71. Ahmad, K. & Henikoff, S. Epigenetic consequences of nucleosome dynamics. Cell 111, 281–284 (2002).

    Article  CAS  PubMed  Google Scholar 

  72. 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 

  73. Eddy, S. R. Non-coding RNA genes and the modern RNA world. Nature Rev. Genet. 2, 919–929 (2001).

    Article  CAS  PubMed  Google Scholar 

  74. Storz, G. An expanding universe of noncoding RNAs. Science 296, 1260–1263 (2002).

    Article  CAS  PubMed  Google Scholar 

  75. Zamore, P. D. Ancient pathways programmed by small RNAs. Science 296, 1265–1269 (2002).

    Article  CAS  PubMed  Google Scholar 

  76. Finnegan, E. J. & Matzke, M. A. The small RNA world. J. Cell Sci. 116, 4689–4693 (2003).

    Article  CAS  PubMed  Google Scholar 

  77. Park, Y. & Kuroda, M. I. Epigenetic aspects of X-chromosome dosage compensation. Science 293, 1083–1085 (2001).

    Article  CAS  PubMed  Google Scholar 

  78. Matzke, M., Matzke, A. J. & Kooter, J. M. RNA: guiding gene silencing. Science 293, 1080–1083 (2001).

    Article  CAS  PubMed  Google Scholar 

  79. Verheggen, C., Le Panse, S., Almouzni, G. & Hernandez-Verdun, D. Maintenance of nucleolar machineries and pre-rRNAs in remnant nucleolus of erythrocyte nuclei and remodeling in Xenopus egg extracts. Exp. Cell Res. 269, 23–34 (2001).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  81. Hall, I. M. et al. Establishment and maintenance of a heterochromatin domain. Science 297, 2232–2237 (2002).

    Article  CAS  PubMed  Google Scholar 

  82. Hall, I. M., Noma, K. & Grewal, S. I. RNA interference machinery regulates chromosome dynamics during mitosis and meiosis in fission yeast. Proc. Natl Acad. Sci. USA 100, 193–198 (2003).

    Article  CAS  PubMed  Google Scholar 

  83. Volpe, T. et al. RNA interference is required for normal centromere function in fission yeast. Chromosome Res. 11, 137–146 (2003). References 81 and 83 demonstrate links between the RNA interference pathway and heterochromatin silencing in fission yeast.

    Article  CAS  PubMed  Google Scholar 

  84. Ramsahoye, B. H. et al. Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc. Natl Acad. Sci. USA 97, 5237–5242 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Reinhart, B. J. & Bartel, D. P. Small RNAs correspond to centromere heterochromatic repeats. Science 297, 1831 (2002).

    Article  CAS  PubMed  Google Scholar 

  86. Martienssen, R. A. Maintenance of heterochromatin by RNA interference of tandem repeats. Nature Genet. 35, 213–214 (2003).

    Article  CAS  PubMed  Google Scholar 

  87. Schramke, V. & Allshire, R. Hairpin RNAs and retrotransposon LTRs effect RNAi and chromatin-based gene silencing. Science 301, 1069–1074 (2003).

    Article  CAS  PubMed  Google Scholar 

  88. 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 

  89. Carmell, M. A., Xuan, Z., Zhang, M. Q. & Hannon, G. J. The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Genes Dev. 16, 2733–2742 (2002).

    Article  CAS  PubMed  Google Scholar 

  90. Stein, P., Svoboda, P., Anger, M. & Schultz, R. M. RNAi: mammalian oocytes do it without RNA-dependent RNA polymerase. RNA 9, 187–192 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Xu, G. L. et al. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 402, 187–191 (1999).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  93. Jackson, J. P., Lindroth, A. M., Cao, X. & Jacobsen, S. E. Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase. Nature 416, 556–560 (2002).

    Article  CAS  PubMed  Google Scholar 

  94. Soppe, W. J. et al. DNA methylation controls histone H3 lysine 9 methylation and heterochromatin assembly in Arabidopsis. Embo J. 21, 6549–6559 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Billy, E., Brondani, V., Zhang, H., Muller, U. & Filipowicz, W. Specific interference with gene expression induced by long, double-stranded RNA in mouse embryonal teratocarcinoma cell lines. Proc. Natl Acad. Sci. USA 98, 14428–14433 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Misteli, T. The concept of self-organization in cellular architecture. J. Cell Biol. 155, 181–185 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Tagami, H., Ray-Gallet, D., Almouzni, G. & Nakatani, Y. Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent on DNA synthesis. Cell 116, 51–61 (2004). This paper describes how histones H3.1 and H3.3 are deposited into chromatin through distinct pathways.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank E. Heard for discussions and her helpful comments on the review, and R. Martienssen for his comments on the figures. The team of G.A. is supported by grants from Programme Collaboratif Institut Curie/Commissariat à l'Energie Atomique, la Ligue Nationale contre le Cancer (Equipe labellisée la Ligue), Euratom, the Commissariat à l'Energie Atomique and the Research Training Network (RTN).

Author information

Authors and Affiliations

  1. Unité Mixte de Reserche 218 Centre National de la Recherche Scientifique/Institut Curie-Section de Recherche, 26 rue d'Ulm, Paris, 75231, Cedex 05, France

    Christèle Maison & Geneviève Almouzni

Authors
  1. Christèle Maison
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Geneviève Almouzni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Geneviève Almouzni.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

Flybase

Mof

roX2

LocusLink

Suv39H1

Suv39H2

Xist

Schizosaccharomyces pombe gene database

Ago1

Clr4

Dcr1

Rdp1

Swi6

Swiss-Prot

HP1α

HP1β

Hp1γ

p150

PCNA

FURTHER INFORMATION

Geneviève Almounzi's laboratory

Functional organization of the genome — chromatin

Nuclear protein database

Glossary

EUCHROMATIN

A form of chromatin that is de-condensed during interphase.

KINETOCHORE

A multiprotein complex that assembles on centromeric DNA and mediates the attachment and movement of chromosomes along the microtubules of the mitotic spindle.

CHROMOCENTRE

Aggregates of centromere from different chromosomes.

PERICENTRIC HETEROCHROMATIN

A region of chromatin that is found juxtaposed to the centromere and that remains condensed throughout the cell cycle. It is considered to be typical constitutive heterochromatin.

SATELLITE REPEAT

A specific DNA sequence that is repeated many times in a long tandem array.

POSITION-EFFECT VARIEGATION

The heritable suppression of genes that results from their abnormal translocation to a position close to heterochromatin.

CHROMODOMAIN

A highly conserved protein-sequence motif that is common to many chromosomal proteins. In HP1 it is crucial for the interaction with histone H3 that is methylated at lysine 9.

CHROMOSHADOW DOMAIN

A protein-sequence motif that is related to the chromodomain in its amino-acid sequence and has so far only been found in the HP1 family of proteins.

HISTONE-CODE HYPOTHESIS

A hypothesis that proposes that distinct histone modifications, on one or more tails, function sequentially, or in combination, to define a code that is translated by effector proteins with specific biological functions.

DOSAGE COMPENSATION

A process by which the expression of sex-linked genes is equalized in species in which males and females differ in the number of sex chromosomes. In Drosophila melanogaster dosage compensation is achieved by hypertranscription of the single male X chromosome.

X INACTIVATION

A process by which dosage compensation in mammals is achieved by the transcriptional silencing of one of the X chromosomes in XX females.

RNA INTERFERENCE

(RNAi). A post-transcriptional gene-silencing process in which double-stranded RNA triggers the degradation of homologous mRNA.

ARGONAUTE

A family of proteins that are characterized by the presence of two homology domains (PAZ and PIWI) that are essential for the production or function of small interfering RNAs. So far, their biochemical function has not been characterized.

DICER

An RNaseIII-type nuclease that is required for the processing of double-stranded-RNA precursors into small interfering RNAs.

RNA-DEPENDENT RNA POLYMERASE

(Rdp1). An unusual RNA polymerase that uses small interfering RNAs as primers to generate long double-stranded RNA, which in turn can be processed by Dicer.

SMALL INTERFERING RNA

(siRNA). During RNA interference, these non-coding RNAs (around 22 nucleotides long) are derived from the processing of long double-stranded RNA. They direct the destruction of mRNA targets that have the same sequence.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maison, C., Almouzni, G. HP1 and the dynamics of heterochromatin maintenance. Nat Rev Mol Cell Biol 5, 296–305 (2004). https://doi.org/10.1038/nrm1355

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm1355

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