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. 1999 Jun;152(2):595–604. doi: 10.1093/genetics/152.2.595

Pairing-dependent mislocalization of a Drosophila brown gene reporter to a heterochromatic environment.

G L Sass 1, S Henikoff 1
PMCID: PMC1460634  PMID: 10353902

Abstract

We describe the precise positioning of a reporter gene within heterochromatin where it may be silenced. A transposition of the 59E-60A region into pericentric heterochromatin ensnares distal 59E-60A via somatic pairing. The frequency with which a brown (bw) reporter gene in 59E is silenced is influenced by chromosomal configurations. Silencing occurs only when the bw+ reporter is unpaired due to heterozygosity with a deficiency, where the frequency of bw+ reporter expression is correlated with the extent of bw gene and flanking sequence present. Surprisingly, the frequency of pairing between the transposition in heterochromatin and distal 59E observed cytologically is indistinguishable from the frequency of pairing of homologous chromosomes at 59E in wild-type larval brains, regardless of configuration. Therefore, bringing a susceptible reporter gene into close proximity with heterochromatin does not necessarily affect its expression, but local pairing changes resulting from altered chromosomal configurations can lead to silencing. We also find that an ensnared distal copy of bw that is interrupted by a heterochromatic insertion enhances silencing. This demonstrates that bw can be simultaneously acted upon by pericentric and distal blocks of heterochromatin.

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Selected References

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  1. Brown K. E., Guest S. S., Smale S. T., Hahm K., Merkenschlager M., Fisher A. G. Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin. Cell. 1997 Dec 12;91(6):845–854. doi: 10.1016/s0092-8674(00)80472-9. [DOI] [PubMed] [Google Scholar]
  2. Csink A. K., Henikoff S. Genetic modification of heterochromatic association and nuclear organization in Drosophila. Nature. 1996 Jun 6;381(6582):529–531. doi: 10.1038/381529a0. [DOI] [PubMed] [Google Scholar]
  3. Csink A. K., Henikoff S. Large-scale chromosomal movements during interphase progression in Drosophila. J Cell Biol. 1998 Oct 5;143(1):13–22. doi: 10.1083/jcb.143.1.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dernburg A. F., Broman K. W., Fung J. C., Marshall W. F., Philips J., Agard D. A., Sedat J. W. Perturbation of nuclear architecture by long-distance chromosome interactions. Cell. 1996 May 31;85(5):745–759. doi: 10.1016/s0092-8674(00)81240-4. [DOI] [PubMed] [Google Scholar]
  5. Dobie K. W., Lee M., Fantes J. A., Graham E., Clark A. J., Springbett A., Lathe R., McClenaghan M. Variegated transgene expression in mouse mammary gland is determined by the transgene integration locus. Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6659–6664. doi: 10.1073/pnas.93.13.6659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dorer D. R., Henikoff S. Transgene repeat arrays interact with distant heterochromatin and cause silencing in cis and trans. Genetics. 1997 Nov;147(3):1181–1190. doi: 10.1093/genetics/147.3.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dreesen T. D., Henikoff S., Loughney K. A pairing-sensitive element that mediates trans-inactivation is associated with the Drosophila brown gene. Genes Dev. 1991 Mar;5(3):331–340. doi: 10.1101/gad.5.3.331. [DOI] [PubMed] [Google Scholar]
  8. Dreesen T. D., Johnson D. H., Henikoff S. The brown protein of Drosophila melanogaster is similar to the white protein and to components of active transport complexes. Mol Cell Biol. 1988 Dec;8(12):5206–5215. doi: 10.1128/mcb.8.12.5206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Eissenberg J. C., Morris G. D., Reuter G., Hartnett T. The heterochromatin-associated protein HP-1 is an essential protein in Drosophila with dosage-dependent effects on position-effect variegation. Genetics. 1992 Jun;131(2):345–352. doi: 10.1093/genetics/131.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Festenstein R., Tolaini M., Corbella P., Mamalaki C., Parrington J., Fox M., Miliou A., Jones M., Kioussis D. Locus control region function and heterochromatin-induced position effect variegation. Science. 1996 Feb 23;271(5252):1123–1125. doi: 10.1126/science.271.5252.1123. [DOI] [PubMed] [Google Scholar]
  11. Geyer P. K., Green M. M., Corces V. G. Tissue-specific transcriptional enhancers may act in trans on the gene located in the homologous chromosome: the molecular basis of transvection in Drosophila. EMBO J. 1990 Jul;9(7):2247–2256. doi: 10.1002/j.1460-2075.1990.tb07395.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gindhart J. G., Jr, Kaufman T. C. Identification of Polycomb and trithorax group responsive elements in the regulatory region of the Drosophila homeotic gene Sex combs reduced. Genetics. 1995 Feb;139(2):797–814. doi: 10.1093/genetics/139.2.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Henikoff S. Dosage-dependent modification of position-effect variegation in Drosophila. Bioessays. 1996 May;18(5):401–409. doi: 10.1002/bies.950180510. [DOI] [PubMed] [Google Scholar]
  14. Jack J. W., Judd B. H. Allelic pairing and gene regulation: A model for the zeste-white interaction in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1368–1372. doi: 10.1073/pnas.76.3.1368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kapoun A. M., Kaufman T. C. Regulatory regions of the homeotic gene proboscipedia are sensitive to chromosomal pairing. Genetics. 1995 Jun;140(2):643–658. doi: 10.1093/genetics/140.2.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lamond A. I., Earnshaw W. C. Structure and function in the nucleus. Science. 1998 Apr 24;280(5363):547–553. doi: 10.1126/science.280.5363.547. [DOI] [PubMed] [Google Scholar]
  17. Lindsley D L, Edington C W, Von Halle E S. Sex-Linked Recessive Lethals in Drosophila Whose Expression Is Suppressed by the Y Chromosome. Genetics. 1960 Dec;45(12):1649–1670. doi: 10.1093/genetics/45.12.1649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Marshall W. F., Dernburg A. F., Harmon B., Agard D. A., Sedat J. W. Specific interactions of chromatin with the nuclear envelope: positional determination within the nucleus in Drosophila melanogaster. Mol Biol Cell. 1996 May;7(5):825–842. doi: 10.1091/mbc.7.5.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Martin-Morris L. E., Loughney K., Kershisnik E. O., Poortinga G., Henikoff S. Characterization of sequences responsible for trans-inactivation of the Drosophila brown gene. Cold Spring Harb Symp Quant Biol. 1993;58:577–584. doi: 10.1101/sqb.1993.058.01.064. [DOI] [PubMed] [Google Scholar]
  20. Martin D. I., Whitelaw E. The vagaries of variegating transgenes. Bioessays. 1996 Nov;18(11):919–923. doi: 10.1002/bies.950181111. [DOI] [PubMed] [Google Scholar]
  21. Milot E., Strouboulis J., Trimborn T., Wijgerde M., de Boer E., Langeveld A., Tan-Un K., Vergeer W., Yannoutsos N., Grosveld F. Heterochromatin effects on the frequency and duration of LCR-mediated gene transcription. Cell. 1996 Oct 4;87(1):105–114. doi: 10.1016/s0092-8674(00)81327-6. [DOI] [PubMed] [Google Scholar]
  22. Morris J. R., Chen J. L., Geyer P. K., Wu C. T. Two modes of transvection: enhancer action in trans and bypass of a chromatin insulator in cis. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10740–10745. doi: 10.1073/pnas.95.18.10740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Park P. C., De Boni U. A specific conformation of the territory of chromosome 17 locates ERBB-2 sequences to a DNase-hypersensitive domain at the nuclear periphery. Chromosoma. 1998 May;107(2):87–95. doi: 10.1007/s004120050284. [DOI] [PubMed] [Google Scholar]
  24. Sigrist C. J., Pirrotta V. 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. 1997 Sep;147(1):209–221. doi: 10.1093/genetics/147.1.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Slatis H M. Position Effects at the Brown Locus in Drosophila Melanogaster. Genetics. 1955 Jan;40(1):5–23. doi: 10.1093/genetics/40.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wakimoto B. T., Hearn M. G. The effects of chromosome rearrangements on the expression of heterochromatic genes in chromosome 2L of Drosophila melanogaster. Genetics. 1990 May;125(1):141–154. doi: 10.1093/genetics/125.1.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wallrath L. L. Unfolding the mysteries of heterochromatin. Curr Opin Genet Dev. 1998 Apr;8(2):147–153. doi: 10.1016/s0959-437x(98)80135-4. [DOI] [PubMed] [Google Scholar]
  28. Weiler K. S., Wakimoto B. T. Heterochromatin and gene expression in Drosophila. Annu Rev Genet. 1995;29:577–605. doi: 10.1146/annurev.ge.29.120195.003045. [DOI] [PubMed] [Google Scholar]

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