Skip to main content
Log in

Drosophila Telomeric Transgenes Provide Insights on Mechanisms of Gene Silencing

  • Published:
Genetica Aims and scope Submit manuscript

Abstract

A significant fraction of most eukaryotic genomes is packaged into chromatin that is not permissive for gene expression. This silent chromatin is typically located near centromeres and telomeres and has fascinated scientists for more than 70 years, yet many questions remain unanswered. Part of the difficulties in studying silent chromatin at the molecular level is the repetitive nature of the DNA sequences in these regions. To overcome this problem, Drosophilastocks carrying in vitrodesigned transgenes inserted within silent chromatin have been generated. Molecular analysis of these transgenes has shed light on the nature of the chromatin structure within these regions and provided insights on the mechanisms of gene silencing. This review will focus on recent studies using telomeric transgenes. The results from these studies suggest that nuclear organization plays a role in gene silencing and that silencing is the result of a block early in the process of transcription initiation.

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

Access this article

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, R.C., E.R. Nimmo, K. Ekwall, J.P. Javerzat & G. Cranston, 1995. Mutations derepressing silent centromeric domains in fission yeast disrupt chromosome segregation. Genes Dev. 9: 218–233.

    PubMed  CAS  Google Scholar 

  • Aparicio, O.M., B.L. Billington & D.E. Gottschling, 1991. Modifiers of position effect are shared between telomeric and silent mating-type loci in S. cerevisiae. Cell 66: 1279–1287.

    Article  PubMed  CAS  Google Scholar 

  • Boivin, A. & J.M. Dura, 1998. In vivochromatin accessibility correlates with gene silencing in Drosophila. Genetics 150: 1539–1549.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Cartwright, I.L. & S.C.R. Elgin, 1986. Nucleosomal instability and induction of new upstream protein-DNA associations accompany activation of four small heat shock protein genes in Drosophila melanogaster. Mol. Cell. Biol. 6: 779–791.

    PubMed  CAS  Google Scholar 

  • Cartwright, I.L., R.P. Hertzberg, P.B. Dervan & S.C.R. Elgin, 1983. Cleavage of chromatin with methidiumpropyl-EDTA iron(II). Proc. Natl. Acad. Sci. USA 80: 3213–3217.

    Article  PubMed  CAS  Google Scholar 

  • Cockell, M. & S.M. Gasser, 1999. Nuclear compartments and gene regulation. Curr. Opin. Genet. Dev. 9: 199–205.

    Article  PubMed  CAS  Google Scholar 

  • Cryderman, D.E., M.H. Cuaycong, S.C.R. Elgin & L.L. Wallrath, 1998. Characterization of sequences associated with position effect variegation at pericentric sites in Drosophilaheterochromatin. Chromosoma 107: 227–285.

    Article  Google Scholar 

  • Cryderman, D.E., E.J. Morris, H. Biessmann, S.C.R. Elgin & L.L. Wallrath, 1999a. Silencing at Drosophilatelomeres: nuclear organization and chromatin structure play critical roles. EMBO J. 18: 3724–3735.

    Article  PubMed  CAS  Google Scholar 

  • Cryderman, D.E., H. Tang, C. Bell, D.S. Gilmour & L.L. Wallrath, 1999b. Heterochromatic silencing of Drosophilaheat shock genes acts at the level of promoter potentiation. Nuc. Acids Res. 27: 3364–3370.

    Article  CAS  Google Scholar 

  • Csink, A.K. & S. Henikoff, 1996. Genetic modification of heterochromatic association and nuclear organization in Drosophila. Nature 381: 529–655.

    Article  PubMed  CAS  Google Scholar 

  • Dernburg, A.F., K.W. Broman, J.C. Fung, W.F. Marshall, J. Philips, D.A. Agard & J.W. Sedat, 1996. Perturbation of nuclear architecture by long-distance chromosome interactions. Cell 85: 745–759.

    Article  PubMed  CAS  Google Scholar 

  • Dobie, K., M. Mehtali, M. McClenaghan & R. Lathe, 1997. Variegated gene expression in mice. Trends Genet. 13: 127–130.

    Article  PubMed  CAS  Google Scholar 

  • Ekwall, K., G. Cranston & R.C. Allshire, 1999. Fission yeast mutants that alleviate transcriptional silencing in centromeric flanking repeats and disrupt chromosome segregation. Genetics 153: 1153–1169.

    PubMed  CAS  Google Scholar 

  • Fanti, L., G. Giovinazzo, M. Berloco & S. Pimpinelli, 1998. The heterochromatin protein 1 (HP1) prevents telomere fusions in Drosophila melanogaster. Mol. Cell 2: 527–538.

    Article  PubMed  CAS  Google Scholar 

  • Farkas, G., J. Gausz, M. Galloni, G. Reuter, H. Gyurkovics & F. Karch, 1994. The Trithorax-likegene encodes the DrosophilaGAGA factor. Nature 371: 806–808.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Gottschling, D.E., O.M. Aparicio, B.L. Billington & V.A. Zakian, 1990. Position effect at S. cerevisiaetelomeres: reversible repression of Pol II transcription. Cell 63: 751–762.

    Article  PubMed  CAS  Google Scholar 

  • Granok, H., B.A. Leibovitch, C.D. Shaffer & S.C.R. Elgin, 1995. Chromatin. Ga-ga over GAGA factor. Curr. Biol. 5: 238–241.

    Article  PubMed  CAS  Google Scholar 

  • Hamiche, A., R. Sandaltzopoulos, D.A. Gdula & C. Wu, 1999. ATPdependent histone octamer sliding mediated by the chromatin remodeling complex NURF. Cell 97: 833–842.

    Article  PubMed  CAS  Google Scholar 

  • Hennig, W., 1999. Heterochromatin chromosoma 108: 1–9.

  • Hochstrasser, M., D. Mathog, Y. Gruenbaum, H. Saumweber & J.W. Sedat, 1986. Spatial organization of chromosomes in the salivary gland nuclei of Drosophila melanogaster. J. Cell Biol. 102: 112–123.

    Article  PubMed  CAS  Google Scholar 

  • James, T.C., J.C. Eissenberg, C. Craig, V. Dietrich, A. Hobson & S.C.R. Elgin, 1989. Distribution patterns of HP1, a heterochromatin-associated nonhistone chromosomal protein of Drosophila. Eur. J. Cell Biol. 50: 170–180.

    PubMed  CAS  Google Scholar 

  • Karpen, G.H. & A.C. Spradling, 1992. Analysis of subtelomeric heterochromatin in the Drosophilaminichromosome Dp1187by single Pelement insertional mutagenesis. Genetics 132: 737–753.

    PubMed  CAS  Google Scholar 

  • Kleinjan, D.J. & V. van Heyningen, 1998. Position effect in human genetic disease. Hum. Mol. Genet. 7: 1611–1618.

    Article  PubMed  CAS  Google Scholar 

  • Koonin, E.V., S. Zhou & J.C. Lucchesi, 1995. The chromo superfamily: new members, duplication of the chromo domain and possible role in delivering transcription regulators to chromatin. Nuc. Acids Res.23: 4229–4233.

    CAS  Google Scholar 

  • Kurenova, E.V., B.A. Leibovich, I.A. Bass, D.V. Bebikhov, M.N. Pavlova & O.N. Danilevskaia, 1990. Hoppel-family of mobile elements of Drosophila melanogaster, flanked by short inverted repeats and having preferential localization in the heterochromatin regions of the genome. Genetika 26: 1701–1712.

    PubMed  CAS  Google Scholar 

  • Levis, R.W., R. Ganesan, K. Houtchens, L.A. Tolar & F.M. Sheen, 1993. Transposons in place of telomeric repeats at a Drosophilatelomere. Cell 75: 1083–1093.

    Article  PubMed  CAS  Google Scholar 

  • Locke, J., L.T. Howard, N. Aippersbach, L. Podemski & R.B. Hodgetts, 1999. The characterization of DINE-1, a short, interspersed repetitive element present on chromosome and in the centric heterochromatin of Drosophila melanogaster. Chromosoma 108: 356–366.

    Article  PubMed  CAS  Google Scholar 

  • Locke, J. & H.E. McDermid, 1993. Analysis of Drosophilachromosome 4 using pulsed field gel electrophoresis. Chromosoma 102: 718–723.

    Article  PubMed  CAS  Google Scholar 

  • Lu, Q., L.L. Wallrath & S.C.R. Elgin, 1995. The role of a positioned nucleosome at the Drosophila melanogaster hsp26promoter. EMBO J. 14: 4738–4746.

    PubMed  CAS  Google Scholar 

  • Lu, Q., L.L. Wallrath, H. Granok & S.C.R. Elgin, 1993. (CT)n:(GA)nrepeats and heat shock elements have distinct roles in chromatin structure and transcriptional activation of the Drosophila hsp26gene. Mol. Cell. Biol. 13: 2802–2814.

    PubMed  CAS  Google Scholar 

  • Miklos, G.L., M.T. Yamamoto, J. Davies & V. Pirrotta, 1988. Microcloning reveals a high frequency of repetitive sequences characteristic of chromosome 4 and the beta-heterochromatin of Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 85: 2051–2055.

    Article  PubMed  CAS  Google Scholar 

  • Nightingale, K.P., R.E. Wellinger, J.M. Sogo & P.B. Becker, 1998. Histone acetylation facilitates RNA polymerase II transcription of the Drosophila hsp26gene in chromatin. EMBO J. 17: 2865–2876.

    Article  PubMed  CAS  Google Scholar 

  • Pardue, M.L. & P.G. DeBaryshe, 1999. Telomeres and telomerase: more than the end of the line. Chromosoma 108: 73–82.

    Article  PubMed  CAS  Google Scholar 

  • Pimpinelli, S., M. Berloco, L. Fanti, P. Dimitri, S. Bonaccorsi, E. Marchetti, R. Caizzi, C. Caggese & M. Gatti, 1995. Transposable elements are stable structural components of Drosophila melanogasterheterochromatin. Proc. Natl. Acad. Sci. USA 92: 3804–3808.

    Article  PubMed  CAS  Google Scholar 

  • Pirrotta, V., 1998. Polycombing the genome: PcG, trxG, and chromatin silencing. Cell 93: 333–336.

    Article  PubMed  CAS  Google Scholar 

  • Platero, J.S., A.K. Csink, A. Quintanilla & S. Henikoff, 1998. Changes in chromosomal localization of heterochromatinbinding proteins during the cell cycle in Drosophila. J. Cell BIol. 140: 1297–1306.

    Article  PubMed  CAS  Google Scholar 

  • Purnell, B.A., P.A. Emanuel & D.S. Gilmour, 1994. TFIID sequence recognition of the initiator and sequences farther downstream in Drosophilaclass II genes. Genes Dev. 8: 830–842.

    PubMed  CAS  Google Scholar 

  • Rastelli, L., C.S. Chan & V. Pirrotta, 1993. Related chromosome binding sites for zeste, suppressors of zeste and Polycomb group proteins in Drosphilaand their dependence on Enhancer of zeste function. EMBO J. 12: 1513–1522.

    PubMed  CAS  Google Scholar 

  • Ravindra, A., K. Weiss & R.T. Simpson, 1999. High-resolution structural analysis of chromatin at specific loci: Saccharomyces cerevisiaesilent mating-type locus HMR?. Mol. Cell. Biol. 19: 7944–7950.

    PubMed  CAS  Google Scholar 

  • Robertson, H.M., C.R. Preston, R.W. Phillis, D.M. Johnson-Schlitz, W.K. Benz & W.R. Engels, 1988. A stable genomic source of Pelement transposase in Drosophila melanogaster. Genetics 118: 461–470.

    PubMed  CAS  Google Scholar 

  • Rougvie, A.E. & J.T. Lis, 1990. Postinitiation transcriptional control in Drosophila melanogaster. Mol. Cell. Biol. 10: 6041–6045.

    PubMed  CAS  Google Scholar 

  • Rubin, G.M. & A.C. Spradling, 1982. Genetic transformation of Drosophilawith transposable element vectors. Science 218: 348–353.

    PubMed  CAS  Google Scholar 

  • Sheen, F.M. & R.W. Levis, 1994. Transposition of the LINE-like retrotransposon TARTto Drosophilachromosome termini. Proc. Natl. Acad. USA 91: 12510–12514.

    Article  CAS  Google Scholar 

  • Sinclair, D.A., N.J. Clegg, J. Antonchuk, T.A. Milne, K. Stankunas, C. Ruse, T.A. Grigliatti, J.A. Kassis & H.W. Brock, 1998. Enhancer of Polycombis a suppressor of position-effect variegation in Drosophila melanogaster. Genetics 148: 211–220.

    PubMed  CAS  Google Scholar 

  • Singh, P.B., J.R. Miller, J. Pearce, R. Kothary, R.D. Burton, R. Paro, T.C. James & S.J. Gaunt, 1991. A sequence motif found in a Drosophilaheterochromatin protein is conserved in animals and plants. Nuc. Acids Res. 19: 789–794.

    CAS  Google Scholar 

  • Thomas, G.H. & S.C.R. Elgin, 1988. Protein/DNA architecture of the DNase I hypersensitive region of the Drosophila hsp26promoter. EMBO J. 7: 2191–2201.

    PubMed  CAS  Google Scholar 

  • Tsukiyama, T. & C. Wu, 1997. Chromatin remodeling and transcription. Curr. Opin. Genet. Dev. 7: 182–191.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Wallrath, L.L., 1998. Unfolding the mysteries of heterochromatin. Curr. Opin. Genet. Dev. 8: 147–153.

    Article  PubMed  CAS  Google Scholar 

  • Wallrath, L.L. & S.C.R. Elgin, 1995. Position effect variegation in Drosophilais associated with an altered chromatin structure. Genes Dev. 9: 1263–1277.

    PubMed  CAS  Google Scholar 

  • Wallrath, L.L., V.P. Guntur, L.E. Rosman & S.C.R. Elgin, 1996. DNA representation of variegating heterochromatic P-element inserts in diploid and polytene tissues of Drosophila melanogaster. Chromosoma 104: 519–527.

    PubMed  CAS  Google Scholar 

  • Walter, M.F., C. Jang, B. Kasravi, J. Donath, B.M. Mechler, J.M. Mason & H. Biessmann, 1995. DNA organization and polymorphism of a wild-type Drosophilatelomere region. Chromosoma 104: 229–241.

    PubMed  CAS  Google Scholar 

  • Weiler, K.S. & B.T. Wakimoto, 1995. Heterochromatin and gene expression in Drosophila. Ann. Rev. Genet. 29: 577–605.

    Article  PubMed  CAS  Google Scholar 

  • Weiss, K. & R.T. Simpson, 1998. High-resolution structural analysis of chromatin at specific loci: Saccharomyces cerevisiaesilent mating type locus HML?. Mol. Cell. Biol. 18: 5392–5403.

    PubMed  CAS  Google Scholar 

  • Wilkins, R.C. & J.T. Lis, 1997. Dynamics of potentiation and activation: GAGA factor and its role in heat shock gene regulation. Nuc. Acids Res. 25: 3963–3968.

    Article  CAS  Google Scholar 

  • Wu, C.-T. & M. Howe, 1995. A genetic analysis of the Suppressor 2 of zestecomplex of Drosophila melanogaster. Genetics 140: 139–181.

    PubMed  CAS  Google Scholar 

  • Zhang, P. & A.C. Spradling, 1995. The Drosophilasalivary gland chromocenter contains highly polytenized subdomains of mitotic heterochromatin. Genetics 139: 659–670.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wallrath, L.L. Drosophila Telomeric Transgenes Provide Insights on Mechanisms of Gene Silencing. Genetica 109, 25–33 (2000). https://doi.org/10.1023/A:1026556705137

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026556705137

Navigation