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Conserved domains control heterochromatin localization and silencing properties of SU(VAR)3–7

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Abstract

The Drosophila protein SU(VAR)3–7 is essential for fly viability, chromosome structure, and heterochromatin formation. We report that searches in silico and in vitro for homologues of SU(VAR)3–7 were successful within, but not outside, the Drosophila genus. Protein sequence homology between the distant sibling species Drosophila melanogaster and Drosophila virilis is low, except for the general organization of the protein and three conserved motives: seven widely spaced zinc fingers in the N-terminal half and the BESS and BoxA motives in the C-terminal half of the protein. We have undertaken a fine functional dissection of SU(VAR)3–7 in vivo using transgenes encoding truncations of the protein. BESS mediates interaction of SU(VAR)3–7 with itself, and BoxA is required for specific heterochromatin association. Both are necessary for the silencing properties of SU(VAR)3–7. The seven zinc fingers, widely spaced over the N-terminal half of SU(VAR)3–7, are required for binding to polytene chromosomes. One finger is necessary and sufficient to determine the appropriate chromatin association of the C-terminal half of the protein. Conferring a function to each of the conserved motives allows us to better understand the mode of action of SU(VAR)3–7 in triggering heterochromatin formation and subsequent genomic silencing.

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References

  • Akam M, Averof M, Castelli-Gair J, Dawes R, Falciani F, Ferrier D (1994) The evolving role of Hox genes in arthropods. Dev Suppl:209–215

  • Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402

    Article  PubMed  CAS  Google Scholar 

  • Barrett SD (2002) Software for scanning microscopy. Proc R Microsc Soc 37:7–14

    Google Scholar 

  • Barrett SD, de Carvalho CR (2003) A software tool to straighten curved chromosome images. Chromosome Res 11:83–88

    Article  PubMed  CAS  Google Scholar 

  • Bhaskar V, Courey AJ (2002) The MADF-BESS domain factor Dip3 potentiates synergistic activation by dorsal and Twist. Gene 299:173–184

    Article  PubMed  CAS  Google Scholar 

  • Brasher SV, Smith BO, Fogh RH, Nietlispach D, Thiru A, Nielsen PR, Broadhurst RW, Ball LJ, Murzina NV, Laue ED (2000) The structure of mouse HP1 suggests a unique mode of single peptide recognition by the shadow chromo domain dimer. EMBO J 19:1587–1597

    Article  PubMed  CAS  Google Scholar 

  • Cléard F, Spierer P (2001) Position-effect variegation in Drosophila: the modifier Su(var)3–7 is a modular DNA-binding protein. EMBO Rep 2:1095–1110

    Article  PubMed  Google Scholar 

  • Cléard F, Matsarskaia M, Spierer P (1995) The modifier of position-effect variegation Suvar(3)7 of Drosophila: there are two alternative transcripts and seven scattered zinc fingers, each preceded by a tryptophan box. Nucleic Acids Res 23:796–802

    Article  PubMed  Google Scholar 

  • Cléard F, Delattre M, Spierer P (1997) SU(VAR)3–7, a Drosophila heterochromatin-associated protein and companion of HP1 in the genomic silencing of position-effect variegation. EMBO J 16:5280–5528

    Article  PubMed  Google Scholar 

  • Delattre M, Spierer A, Tonka CH, Spierer P (2000) The genomic silencing of position-effect variegation in Drosophila melanogaster: interaction between the heterochromatin-associated proteins Su(var)3–7 and HP1. J Cell Sci 113:4253–4261

    PubMed  CAS  Google Scholar 

  • Delattre M, Spierer A, Hulo N, Spierer P (2002) A new gene in Drosophila melanogaster, Ravus, the phantom of the modifier of position-effect variegation Su(var)3–7. Int J Dev Biol 46:167–171

    PubMed  CAS  Google Scholar 

  • Delattre M, Spierer A, Jaquet Y, Spierer P (2004) Increased expression of Drosophila Su(var)3–7 triggers Su(var)3–9-dependent heterochromatin formation. J Cell Sci 117:6239–6247

    Article  PubMed  CAS  Google Scholar 

  • Eissenberg JC, Morris GD, Reuter G, Hartnett T (1992) The heterochromatin-associated protein HP-1 is an essential protein in Drosophila with dosage-dependent effects on position-effect variegation. Genetics 131:345–352

    PubMed  CAS  Google Scholar 

  • Hart CM, Zhao K, Laemmli UK (1997) The scs’ boundary element: characterization of boundary element-associated factors. Mol Cell Biol 17:999–1009

    PubMed  CAS  Google Scholar 

  • Hooper JE, Perez-Alonso M, Bermingham JR, Prout M, Rocklein BA, Wagenbach M, Edstrom JE, de Frutos R, Scott MP (1992) Comparative studies of Drosophila Antennapedia genes. Genetics 132:453–469

    PubMed  CAS  Google Scholar 

  • Jacobs SA, Taverna SD, Zhang Y, Briggs SD, Li J, Eissenberg JC, Allis CD, Khorasanizadeh S (2001) Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3. EMBO J 20:5232–5241

    Article  PubMed  CAS  Google Scholar 

  • Jaquet Y, Delattre M, Spierer A, Spierer P (2002) Functional dissection of the Drosophila modifier of variegation Su(var)3–7. Development 129:3975–3982

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Le Douarin B, Nielsen AL, Garnier JM, Ichinose H, Jeanmougin F, Losson R, Chambon P (1996) A possible involvement of TIF1 alpha and TIF1 beta in the epigenetic control of transcription by nuclear receptors. EMBO J 15:6701–6715

    PubMed  Google Scholar 

  • Li Y, Kirschmann DA, Wallrath LL (2002) Does heterochromatin protein 1 always follow code? Proc Natl Acad Sci U S A 99(Suppl 4):16462–16469

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Danzer JR, Alvarez P, Belmont AS, Wallrath LL (2003) Effects of tethering HP1 to euchromatic regions of the Drosophila genome. Development 130:1817–1824

    Article  PubMed  CAS  Google Scholar 

  • Liang H, Guo W, Nagarajan L (2000) Chromosomal mapping and genomic organization of an evolutionarily conserved zinc finger gene ZNF277. Genomics 66:226–228

    Article  PubMed  CAS  Google Scholar 

  • Looman C, Abrink M, Mark C, Hellman L (2002) KRAB zinc finger proteins: an analysis of the molecular mechanisms governing their increase in numbers and complexity during evolution. Mol Biol Evol 19:2118–2130

    PubMed  CAS  Google Scholar 

  • Nielsen AL, Oulad-Abdelghani M, Ortiz JA, Remboutsika E, Chambon P, Losson R (2001) Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins. Mol Cell 7:729–739

    Article  PubMed  CAS  Google Scholar 

  • Noma K, Sugiyama T, Cam H, Verdel A, Zofall M, Jia S, Moazed D, Grewal SI (2004) RITS acts in cis to promote RNA interference-mediated transcriptional and post-transcriptional silencing. Nat Genet 36:1174–1180

    Article  PubMed  CAS  Google Scholar 

  • Notredame C, Higgins DG, Heringa J (2000) T-coffee: a novel method for fast and accurate multiple sequence alignment. J Mol Biol 302:205–217

    Article  PubMed  CAS  Google Scholar 

  • O’Neil MT, Belote JM (1992) Interspecific comparison of the transformer gene of Drosophila reveals an unusually high degree of evolutionary divergence. Genetics 131:113–128

    PubMed  CAS  Google Scholar 

  • Perrini B, Piacentini L, Fanti L, Altieri F, Chichiarelli S, Berloco M, Turano C, Ferraro A, Pimpinelli S (2004) HP1 controls telomere capping, telomere elongation, and telomere silencing by two different mechanisms in Drosophila. Mol Cell 15:467–476

    Article  PubMed  CAS  Google Scholar 

  • Reuter G, Spierer P (1992) Position effect variegation and chromatin proteins. Bioessays 14:605–612

    Article  PubMed  CAS  Google Scholar 

  • Reuter D, Schuh R, Jackle H (1989) The homeotic gene spalt (sal) evolved during Drosophila speciation. Proc Natl Acad Sci U S A 86:5483–5486

    Article  PubMed  CAS  Google Scholar 

  • Reuter G, Giarre M, Farah J, Gausz J, Spierer A, Spierer P (1990) Dependence of position-effect variegation in Drosophila on dose of a gene encoding an unusual zinc-finger protein. Nature 344:219–223

    Article  PubMed  CAS  Google Scholar 

  • Sander C, Schneider R (1991) Database of homology-derived protein structures and the structural meaning of sequence alignment. Proteins 9:56–68

    Article  PubMed  CAS  Google Scholar 

  • Schmid KJ, Tautz D (1997) A screen for fast evolving genes from Drosophila. Proc Natl Acad Sci U S A 94:9746–9750

    Article  PubMed  CAS  Google Scholar 

  • Schotta G, Ebert A, Krauss V, Fischer A, Hoffmann J, Rea S, Jenuwein T, Dorn R, Reuter G (2002) Central role of Drosophila SU(VAR)3–9 in histone H3-K9 methylation and heterochromatic gene silencing. EMBO J 21:1121–1131

    Article  PubMed  CAS  Google Scholar 

  • Schotta G, Ebert A, Dorn R, Reuter G (2003) Position-effect variegation and the genetic dissection of chromatin regulation in Drosophila. Semin Cell Dev Biol 14:67–75

    Article  PubMed  CAS  Google Scholar 

  • Seum C, Spierer A, Delattre M, Pauli D, Spierer P (2000) A GAL4-HP1 fusion protein targeted near heterochromatin promotes gene silencing. Chromosoma 109:453–459

    Article  PubMed  CAS  Google Scholar 

  • Seum C, Pauli D, Delattre M, Jaquet Y, Spierer A, Spierer P (2002) Isolation of Su(var)3–7 mutations by homologous recombination in Drosophila melanogaster. Genetics 161:1125–1136

    PubMed  CAS  Google Scholar 

  • Sigrist CJ, Pirrotta V (1997) Chromatin insulator elements block the silencing of a target gene by the Drosophila polycomb response element (PRE) but allow trans interactions between PREs on different chromosomes. Genetics 147:209–221

    PubMed  CAS  Google Scholar 

  • Spierer A, Seum C, Delattre M, Spierer P (2005) Loss of the modifiers of variegation Su(var)3–7 or HP1 impacts male X polytene chromosome morphology and dosage compensation. J Cell Sci 118:5047–5057

    Article  PubMed  CAS  Google Scholar 

  • Sun FL, Cuaycong MH, Craig CA, Wallrath LL, Locke J, Elgin SC (2000) The fourth chromosome of Drosophila melanogaster: interspersed euchromatic and heterochromatic domains. Proc Natl Acad Sci U S A 97:5340–5345

    Article  PubMed  CAS  Google Scholar 

  • Tartof KD, Bishop C, Jones M, Hobbs CA, Locke J (1989) Towards an understanding of position effect variegation. Dev Genet 10:162–176

    Article  PubMed  CAS  Google Scholar 

  • Turner BM, Birley AJ, Lavender J (1992) Histone H4 isoforms acetylated at specific lysine residues define individual chromosomes and chromatin domains in Drosophila polytene nuclei. Cell 69:375–384

    Article  PubMed  CAS  Google Scholar 

  • Wallrath LL (1998) Unfolding the mysteries of heterochromatin. Curr Opin Genet Dev 8:147–153

    Article  PubMed  CAS  Google Scholar 

  • Weiler KS, Wakimoto BT (1995) Heterochromatin and gene expression in Drosophila. Annu Rev Genet 29:577–605

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto K, Sonoda M (2003) Self-interaction of heterochromatin protein 1 is required for direct binding to histone methyltransferase, SUV39H1. Biochem Biophys Res Commun 301:287–292

    Article  PubMed  CAS  Google Scholar 

  • Ye Q, Callebaut I, Pezhman A, Courvalin JC, Worman HJ (1997) Domain-specific interactions of human HP1-type chromodomain proteins and inner nuclear membrane protein LBR. J Biol Chem 272:14983–14989

    Article  PubMed  CAS  Google Scholar 

  • Zhao K, Hart CM, Laemmli UK (1995) Visualization of chromosomal domains with boundary element-associated factor BEAF-32. Cell 81:879–889

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Fabienne Cléard and Frédéric Pâques for their contribution to the early part of the search for homologues, François Karch for the Drosophila virilis genomic library, and Chia-Hwa Tonka for her excellent technical help. We thank Karl Matter for HA antibody and Séverine Bontron for comments on the manuscript. This work was supported by the NCCR “Frontiers in genetics” and the State of Geneva.

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Correspondence to Pierre Spierer.

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Communicated by S. Pimpinelli

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Jaquet, Y., Delattre, M., Montoya-Burgos, J. et al. Conserved domains control heterochromatin localization and silencing properties of SU(VAR)3–7. Chromosoma 115, 139–150 (2006). https://doi.org/10.1007/s00412-005-0036-2

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