Skip to main content
SpringerLink
Log in

Heterochromatin assembly: A new twist on an old model

  • Published:
Chromosome Research Aims and scope Submit manuscript

Abstract

The organization of eukaryotic genomes requires a harmony between efficient compaction and accessibility. This is achieved through its packaging into chromatin. Chromatin can be subdivided into two general structural and functional compartments: euchromatin and heterochromatin. Euchromatin comprises most of the expressed genome, while heterochromatin participates intimately in the production of structures such as centromeres and telomeres essential for chromosome function. Studies in the fission yeast Schizosaccharomyces pombe have begun to highlight the genetic pathways critical for the assembly and epigenetic maintenance of heterochromatin, including key roles played by the RNAi machinery, H3 lysine 9 methylation and heterochromatin protein 1 (HP1). Recent studies have also identified a novel E3 ubiquitin ligase universally required for H3 K9 methylation. Here we outline these studies and propose several models for the role of this E3 ligase in heterochromatin assembly.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Allshire RC, Javerzat JP, Redhead NJ, Cranston G (1994) Position effect variegation at fission yeast centromeres. Cell 76: 157–169.

    Article  CAS  PubMed  Google Scholar 

  • Bernard P, Maure JF, Partridge JF, Genier S, Javerzat JP, Allshire RC (2001) Requirement of heterochromatin for cohesion at centromeres. Science 294: 2539–2542.

    Article  CAS  PubMed  Google Scholar 

  • Cam HP, Sugiyama T, Chen ES, Chen X, Fitzgerald PC, Grewal SI (2005) Comprehensive analysis of heterochromatin- and RNAi-mediated epigenetic control of the fission yeast genome. Nat Genet 37: 809–819.

    Article  CAS  PubMed  Google Scholar 

  • Cardozo T, Pagano M (2004) The SCF ubiquitin ligase: insights into a molecular machine. Nat Rev Mol Cell Biol 5: 739–751.

    Article  CAS  PubMed  Google Scholar 

  • Djupedal I, Portoso M, Spahr H et al. (2005) RNA Pol II subunit Rpb7 promotes centromeric transcription and RNAi-directed chromatin silencing. Genes Dev 19: 2301–2306.

    Article  CAS  PubMed  Google Scholar 

  • Doe CL, Wang G, Chow C, Fricker MD, Singh PB, Mellor EJ (1998) The fission yeast chromo domain encoding gene chp1(+) is required for chromosome segregation and shows a genetic interaction with alpha-tubulin. Nucl Acids Res 26: 4222–4229.

    Article  CAS  PubMed  Google Scholar 

  • Ekwall K, Ruusala T (1994) Mutations in rik1, clr2, clr3 and clr4 genes asymmetrically derepress the silent mating-type loci in fission yeast. Genetics 136: 53–64.

    CAS  PubMed  Google Scholar 

  • Fischle W, Wang Y, Jacobs SA, Kim Y, Allis CD, Khorasanizadeh S (2003) Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes Dev 17: 1870–1881.

    Article  CAS  PubMed  Google Scholar 

  • Flick K, Ouni I, Wohlschlegel JA et al. (2004) Proteolysis-independent regulation of the transcription factor Met4 by a single Lys 48-linked ubiquitin chain. Nat Cell Biol 6: 634–641.

    Article  CAS  PubMed  Google Scholar 

  • Grewal SI, Elgin SC (2002) Heterochromatin: new possibilities for the inheritance of structure. Curr Opin Genet Dev 12: 178–187.

    Article  CAS  PubMed  Google Scholar 

  • Grewal SI, Klar AJ (1996) Chromosomal inheritance of epigenetic states in fission yeast during mitosis and meiosis. Cell 86: 95–101.

    Article  CAS  PubMed  Google Scholar 

  • Grewal SI, Bonaduce MJ, Klar AJ (1998) Histone deacetylase homologs regulate epigenetic inheritance of transcriptional silencing and chromosome segregation in fission yeast. Genetics 150: 563–576.

    CAS  PubMed  Google Scholar 

  • Groisman R, Polanowska J, Kuraoka I et al. (2003) The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell 113: 357–367.

    Article  CAS  PubMed  Google Scholar 

  • Hall IM, Shankaranarayana GD, Noma K, Ayoub N, Cohen A, Grewal SI (2002) Establishment and maintenance of a heterochromatin domain. Science 297: 2232–2237.

    Article  CAS  PubMed  Google Scholar 

  • Hall IM, Noma K, Grewal SI (2003) RNA interference machinery regulates chromosome dynamics during mitosis and meiosis in fission yeast. Proc Natl Acad Sci USA 100: 193–198.

    CAS  PubMed  Google Scholar 

  • Hay RT (2005) SUMO: a history of modification. Mol Cell 18: 1–12.

    Article  CAS  PubMed  Google Scholar 

  • Horn PJ, Bastie JN, Peterson CL (2005) A Rik1-associated, cullin-dependent E3 ubiquitin ligase is essential for heterochromatin formation. Genes Dev 19: 1705–1714.

    Article  CAS  PubMed  Google Scholar 

  • Jia S, Noma K, Grewal SI (2004a) RNAi-independent heterochromatin nucleation by the stress-activated ATF/CREB family proteins. Science 304: 1971–1976.

    Article  CAS  PubMed  Google Scholar 

  • Jia S, Yamada T, Grewal SI (2004b) Heterochromatin regulates cell type-specific long-range chromatin interactions essential for directed recombination. Cell 119: 469–480.

    Article  CAS  PubMed  Google Scholar 

  • Jia S, Kobayashi R, Grewal SI (2005) Ubiquitin ligase component Cul4 associates with Clr4 histone methyltransferase to assemble heterochromatin. Nat Cell Biol 7: 1007–1013.

    Article  CAS  PubMed  Google Scholar 

  • Johnson K, Shapiro-Shelef M, Tunyaplin C, Calame K (2005) Regulatory events in early and late B-cell differentiation. Mol Immunol 42: 749–761.

    Article  CAS  PubMed  Google Scholar 

  • Kanoh J, Sadaie M, Urano T, Ishikawa F (2005) Telomere binding protein Taz1 establishes Swi6 heterochromatin independently of RNAi at telomeres. Curr Biol 15: 1808–1819.

    Article  CAS  PubMed  Google Scholar 

  • Kato H, Goto DB, Martienssen RA, Urano T, Furukawa K, Murakami Y (2005) RNA polymerase II is required for RNAi-dependent heterochromatin assembly. Science 309: 467–469.

    Article  CAS  PubMed  Google Scholar 

  • Kim HS, Choi ES, Shin JA, Jang YK, Park SD (2004) Regulation of Swi6/HP1-dependent heterochromatin assembly by cooperation of components of the mitogen-activated protein kinase pathway and a histone deacetylase Clr6. J Biol Chem 279: 42850–42859.

    CAS  PubMed  Google Scholar 

  • Kniola B, O'Toole E, McIntosh JR et al. (2001) The domain structure of centromeres is conserved from fission yeast to humans. Mol Biol Cell 12: 2767–2775.

    CAS  PubMed  Google Scholar 

  • Li F, Goto DB, Zaratiegui M, Tang X, Martienssen R, Cande WZ (2005) Two novel proteins, dos1 and dos2, interact with rik1 to regulate heterochromatic RNA interference and histone modification. Curr Biol 15: 1448–1457.

    CAS  PubMed  Google Scholar 

  • Liu Y, Mochizuki K, Gorovsky MA (2004) Histone H3 lysine 9 methylation is required for DNA elimination in developing macronuclei in Tetrahymena. Proc Natl Acad Sci USA 101: 1679–1684.

    CAS  PubMed  Google Scholar 

  • Motamedi MR, Verdel A, Colmenares SU, Gerber SA, Gygi SP, Moazed D (2004) Two RNAi complexes, RITS and RDRC, physically interact and localize to noncoding centromeric RNAs. Cell 119: 789–802.

    Article  CAS  PubMed  Google Scholar 

  • Muratani M, Kung C, Shokat KM, Tansey WP (2005) The F box protein Dsg1/Mdm30 is a transcriptional coactivator that stimulates Gal4 turnover and cotranscriptional mRNA processing. Cell 120: 887–899.

    Article  CAS  PubMed  Google Scholar 

  • Nakayama J, Klar AJ, Grewal SI (2000) A chromodomain protein, Swi6, performs imprinting functions in fission yeast during mitosis and meiosis. Cell 101: 307–317.

    Article  CAS  PubMed  Google Scholar 

  • Nakayama J, Rice JC, Strahl BD, Allis CD, Grewal SI (2001) Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 292: 110–113.

    Article  CAS  PubMed  Google Scholar 

  • Neuwald AF, Poleksic A (2000) PSI-BLAST searches using hidden markov models of structural repeats: prediction of an unusual sliding DNA clamp and of beta-propellers in UV-damaged DNA-binding protein. Nucleic Acids Res 28: 3570–3580.

    Article  CAS  PubMed  Google Scholar 

  • Nimmo ER, Cranston G, Allshire RC (1994) Telomere-associated chromosome breakage in fission yeast results in variegated expression of adjacent genes. EMBO J 13: 3801–3811.

    CAS  PubMed  Google Scholar 

  • Noma K, Allis CD, Grewal SI (2001) Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science 293: 1150–1155.

    Article  CAS  PubMed  Google Scholar 

  • Noma K, Sugiyama T, Cam H et al. (2004) RITS acts in cis to promote RNA interference-mediated transcriptional and post-transcriptional silencing. Nat Genet 36: 1174–1180.

    Article  CAS  PubMed  Google Scholar 

  • Nonaka N, Kitajima T, Yokobayashi S et al. (2002) Recruitment of cohesin to heterochromatic regions by Swi6/HP1 in fission yeast. Nat Cell Biol 4: 89–93.

    Article  CAS  PubMed  Google Scholar 

  • Obuse C, Yang H, Nozaki N, Goto S, Okazaki T, Yoda K (2004) Proteomics analysis of the centromere complex from HeLa interphase cells: UV-damaged DNA binding protein 1 (DDB-1) is a component of the CEN-complex, while BMI-1 is transiently co-localized with the centromeric region in interphase. Genes Cells 9: 105–120.

    Article  CAS  PubMed  Google Scholar 

  • Osaka F, Saeki M, Katayama S et al. (2000) Covalent modifier NEDD8 is essential for SCF ubiquitin-ligase in fission yeast. EMBO J 19: 3475–3484.

    Article  CAS  PubMed  Google Scholar 

  • Partridge JF, Borgstrom B, Allshire RC (2000) Distinct protein interaction domains and protein spreading in a complex centromere. Genes Dev 14 783–791.

    CAS  PubMed  Google Scholar 

  • Partridge JF, Scott KS, Bannister AJ, Kouzarides T, Allshire RC (2002) Cis-acting DNA from fission yeast centromeres mediates histone H3 methylation and recruitment of silencing factors and cohesin to an ectopic site. Curr Biol 12: 1652–1660.

    Article  CAS  PubMed  Google Scholar 

  • Peng J, Schwartz D, Elias JE et al. (2003) A proteomics approach to understanding protein ubiquitination. Nat Biotechnol 21: 921–926.

    Article  CAS  PubMed  Google Scholar 

  • Petrie VJ, Wuitschick JD, Givens CD, Kosinski AM, Partridge JF (2005) RNA interference (RNAi)-dependent and RNAi-independent association of the Chp1 chromodomain protein with distinct heterochromatic loci in fission yeast. Mol Cell Biol 25: 2331–2346.

    Article  CAS  PubMed  Google Scholar 

  • Petroski MD, Deshaies RJ (2005) Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol 6: 9–20.

    Article  CAS  PubMed  Google Scholar 

  • Pickart CM (2001) Mechanisms underlying ubiquitination. Annu Rev Biochem 70: 503–533.

    Article  CAS  PubMed  Google Scholar 

  • Reinhart BJ, Bartel DP (2002) Small RNAs correspond to centromere heterochromatic repeats. Science 297: 1831.

    Article  CAS  PubMed  Google Scholar 

  • Rogakou EP, Boon C, Redon C, Bonner WM (1999) Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol 146: 905–916.

    Article  CAS  PubMed  Google Scholar 

  • Roguev A, Schaft D, Shevchenko A, Aasland R, Shevchenko A, Stewart AF (2003) High conservation of the Set1/Rad6 axis of histone 3 lysine 4 methylation in budding and fission yeasts. J Biol Chem 278: 8487–8493.

    Article  CAS  PubMed  Google Scholar 

  • Sadaie M, Iida T, Urano T, Nakayama J (2004) A chromodomain protein, Chp1, is required for the establishment of heterochromatin in fission yeast. EMBO J 23: 3825–3835.

    Article  CAS  PubMed  Google Scholar 

  • Schramke V, Sheedy DM, Denli AM et al. (2005) RNA-interference-directed chromatin modification coupled to RNA polymerase II transcription. Nature 435: 1275–1279.

    Article  CAS  PubMed  Google Scholar 

  • Shankaranarayana GD, Motamedi MR, Moazed D, Grewal SI (2003) Sir2 regulates histone H3 lysine 9 methylation and heterochromatin assembly in fission yeast. Curr Biol 13: 1240–1246.

    Article  CAS  PubMed  Google Scholar 

  • Shin JA, Choi ES, Kim HS et al. (2005) SUMO modification is involved in the maintenance of heterochromatin stability in fission yeast. Mol Cell 19: 817–828.

    Article  CAS  PubMed  Google Scholar 

  • Sigova A, Rhind N, Zamore PD (2004) A single Argonaute protein mediates both transcriptional and posttranscriptional silencing in Schizosaccharomyces pombe. Genes Dev 18: 2359–2367.

    Article  CAS  PubMed  Google Scholar 

  • Sullivan BA, Karpen GH (2004) Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin. Nat Struct Mol Biol 11: 1076–1083.

    Article  CAS  PubMed  Google Scholar 

  • Sun L, Chen ZJ (2004) The novel functions of ubiquitination in signaling. Curr Opin Cell Biol 16: 119–126.

    CAS  PubMed  Google Scholar 

  • Sun ZW, Allis CD (2002) Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature 418: 104–108.

    CAS  PubMed  Google Scholar 

  • Thon G, Verhein-Hansen J (2000) Four chromo-domain proteins of Schizosaccharomyces pombe differentially repress transcription at various chromosomal locations. Genetics 155: 551–568.

    CAS  PubMed  Google Scholar 

  • Thon G, Cohen A, Klar AJ (1994) Three additional linkage groups that repress transcription and meiotic recombination in the mating-type region of Schizosaccharomyces pombe. Genetics 138: 29–38.

    CAS  PubMed  Google Scholar 

  • Thon G, Hansen KR, Altes SP et al. (2005) The Clr7 and Clr8 directionality factors and the Pcu4 cullin mediate heterochromatin formation in the fission yeast Schizosaccharomyces pombe. Genetics 171: 1583–1595.

    Google Scholar 

  • Tuzon CT, Borgstrom B, Weilguny D, Egel R, Cooper JP, Nielsen O (2004) The fission yeast heterochromatin protein Rik1 is required for telomere clustering during meiosis. J Cell Biol 165: 759–765.

    Article  CAS  PubMed  Google Scholar 

  • Vakoc CR, Mandat SA, Olenchock BA, Blobel GA (2005) Histone H3 lysine 9 methylation and HP1gamma are associated with transcription elongation through mammalian chromatin. Mol Cell 19: 381–391.

    Article  CAS  PubMed  Google Scholar 

  • Verdel A, Moazed D (2005) RNAi-directed assembly of heterochromatin in fission yeast. FEBS Lett 579: 5872–5878.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Volpe TA, Kidner C, Hall IM, Teng G, Grewal SI, Martienssen RA (2002) Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297: 1833–1837.

    Article  CAS  PubMed  Google Scholar 

  • Volpe T, Schramke V, Hamilton GL et al. (2003) RNA interference is required for normal centromere function in fission yeast. Chromosome Res 11: 137–146.

    Article  CAS  PubMed  Google Scholar 

  • Wood A, Krogan NJ, Dover J et al. (2003) Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter. Mol Cell 11: 267–274.

    Article  CAS  PubMed  Google Scholar 

  • Wysocka J, Swigut T, Milne TA et al. (2005) WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. Cell 121: 859–872.

    Article  CAS  PubMed  Google Scholar 

  • Xhemalce B, Seeler JS, Thon G, Dejean A, Arcangioli B (2004) Role of the fission yeast SUMO E3 ligase Pli1p in centromere and telomere maintenance. EMBO J 23: 3844–3853.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation St., Biotech 2, Suite 210, Worcester, MA, 01605, USA

    Peter J. Horn & Craig L. Peterson

Authors
  1. Peter J. Horn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Craig L. Peterson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Craig L. Peterson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Horn, P.J., Peterson, C.L. Heterochromatin assembly: A new twist on an old model. Chromosome Res 14, 83–94 (2006). https://doi.org/10.1007/s10577-005-1018-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10577-005-1018-1

Key words

Search

Navigation