Skip to main content
Genetics logoLink to Genetics
. 1997 Aug;146(4):1365–1380. doi: 10.1093/genetics/146.4.1365

A Polycomb and Gaga Dependent Silencer Adjoins the Fab-7 Boundary in the Drosophila Bithorax Complex

K Hagstrom 1, M Muller 1, P Schedl 1
PMCID: PMC1208081  PMID: 9258680

Abstract

The homeotic genes of the Drosophila bithorax complex are controlled by a large cis-regulatory region that ensures their segmentally restricted pattern of expression. A deletion that removes the Frontabdominal-7 cis-regulatory region (Fab-7(1)) dominantly transforms parasegment 11 into parasegment 12. Previous studies suggested that removal of a domain boundary element on the proximal side of Fab-7(1) is responsible for this gain-of-function phenotype. In this article we demonstrate that the Fab-7(1) deletion also removes a silencer element, the iab-7 PRE, which maps to a different DNA segment and plays a different role in regulating parasegment-specific expression patterns of the Abd-B gene. The iab-7 PRE mediates pairing-sensitive silencing of mini-white, and can maintain the segmentally restricted expression pattern of a BXD, Ubx/lacZ reporter transgene. Both silencing activities depend upon Polycomb Group proteins. Pairing-sensitive silencing is relieved by removing the transvection protein Zeste, but is enhanced in a novel pairing-independent manner by the zeste(1) allele. The iab-7 PRE silencer is contained within a 0.8-kb fragment that spans a nuclease hypersensitive site, and silencing appears to depend on the chromatin remodeling protein, the GAGA factor.

Full Text

The Full Text of this article is available as a PDF (9.9 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bhat K. M., Farkas G., Karch F., Gyurkovics H., Gausz J., Schedl P. The GAGA factor is required in the early Drosophila embryo not only for transcriptional regulation but also for nuclear division. Development. 1996 Apr;122(4):1113–1124. doi: 10.1242/dev.122.4.1113. [DOI] [PubMed] [Google Scholar]
  2. Biggin M. D., Tjian R. Transcription factors that activate the Ultrabithorax promoter in developmentally staged extracts. Cell. 1988 Jun 3;53(5):699–711. doi: 10.1016/0092-8674(88)90088-8. [DOI] [PubMed] [Google Scholar]
  3. Brand A. H., Breeden L., Abraham J., Sternglanz R., Nasmyth K. Characterization of a "silencer" in yeast: a DNA sequence with properties opposite to those of a transcriptional enhancer. Cell. 1985 May;41(1):41–48. doi: 10.1016/0092-8674(85)90059-5. [DOI] [PubMed] [Google Scholar]
  4. Breen T. R., Duncan I. M. Maternal expression of genes that regulate the bithorax complex of Drosophila melanogaster. Dev Biol. 1986 Dec;118(2):442–456. doi: 10.1016/0012-1606(86)90015-1. [DOI] [PubMed] [Google Scholar]
  5. Busturia A., Bienz M. Silencers in abdominal-B, a homeotic Drosophila gene. EMBO J. 1993 Apr;12(4):1415–1425. doi: 10.1002/j.1460-2075.1993.tb05785.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Casares F., Sánchez-Herrero E. Regulation of the infraabdominal regions of the bithorax complex of Drosophila by gap genes. Development. 1995 Jun;121(6):1855–1866. doi: 10.1242/dev.121.6.1855. [DOI] [PubMed] [Google Scholar]
  7. Chan C. S., Rastelli L., Pirrotta V. A Polycomb response element in the Ubx gene that determines an epigenetically inherited state of repression. EMBO J. 1994 Jun 1;13(11):2553–2564. doi: 10.1002/j.1460-2075.1994.tb06545.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chiang A., O'Connor M. B., Paro R., Simon J., Bender W. Discrete Polycomb-binding sites in each parasegmental domain of the bithorax complex. Development. 1995 Jun;121(6):1681–1689. doi: 10.1242/dev.121.6.1681. [DOI] [PubMed] [Google Scholar]
  9. Chinwalla V., Jane E. P., Harte P. J. The Drosophila trithorax protein binds to specific chromosomal sites and is co-localized with Polycomb at many sites. EMBO J. 1995 May 1;14(9):2056–2065. doi: 10.1002/j.1460-2075.1995.tb07197.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Croston G. E., Kerrigan L. A., Lira L. M., Marshak D. R., Kadonaga J. T. Sequence-specific antirepression of histone H1-mediated inhibition of basal RNA polymerase II transcription. Science. 1991 Feb 8;251(4994):643–649. doi: 10.1126/science.1899487. [DOI] [PubMed] [Google Scholar]
  11. Dimitri P., Pisano C. Position effect variegation in Drosophila melanogaster: relationship between suppression effect and the amount of Y chromosome. Genetics. 1989 Aug;122(4):793–800. doi: 10.1093/genetics/122.4.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dorer D. R., Henikoff S. Expansions of transgene repeats cause heterochromatin formation and gene silencing in Drosophila. Cell. 1994 Jul 1;77(7):993–1002. doi: 10.1016/0092-8674(94)90439-1. [DOI] [PubMed] [Google Scholar]
  13. Farkas G., Gausz J., Galloni M., Reuter G., Gyurkovics H., Karch F. The Trithorax-like gene encodes the Drosophila GAGA factor. Nature. 1994 Oct 27;371(6500):806–808. doi: 10.1038/371806a0. [DOI] [PubMed] [Google Scholar]
  14. Gelbart W. M., Wu C. T. Interactions of zeste mutations with loci exhibiting transvection effects in Drosophila melanogaster. Genetics. 1982 Oct;102(2):179–189. doi: 10.1093/genetics/102.2.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Glaser R. L., Thomas G. H., Siegfried E., Elgin S. C., Lis J. T. Optimal heat-induced expression of the Drosophila hsp26 gene requires a promoter sequence containing (CT)n.(GA)n repeats. J Mol Biol. 1990 Feb 20;211(4):751–761. doi: 10.1016/0022-2836(90)90075-W. [DOI] [PubMed] [Google Scholar]
  16. Gowen J. W., Gay E. H. EFFECT OF TEMPERATURE ON EVERSPORTING EYE COLOR IN DROSOPHILA MELANOGASTER. Science. 1933 Mar 24;77(1995):312–312. doi: 10.1126/science.77.1995.312. [DOI] [PubMed] [Google Scholar]
  17. Granok H., Leibovitch B. A., Shaffer C. D., Elgin S. C. Chromatin. Ga-ga over GAGA factor. Curr Biol. 1995 Mar 1;5(3):238–241. doi: 10.1016/s0960-9822(95)00048-0. [DOI] [PubMed] [Google Scholar]
  18. Gray S., Levine M. Short-range transcriptional repressors mediate both quenching and direct repression within complex loci in Drosophila. Genes Dev. 1996 Mar 15;10(6):700–710. doi: 10.1101/gad.10.6.700. [DOI] [PubMed] [Google Scholar]
  19. Hazelrigg T., Petersen S. An unusual genomic position effect on Drosophila white gene expression: pairing dependence, interactions with zeste, and molecular analysis of revertants. Genetics. 1992 Jan;130(1):125–138. doi: 10.1093/genetics/130.1.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Henikoff S. Position-effect variegation after 60 years. Trends Genet. 1990 Dec;6(12):422–426. doi: 10.1016/0168-9525(90)90304-o. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Jackson M. E. Negative regulation of eukaryotic transcription. J Cell Sci. 1991 Sep;100(Pt 1):1–7. doi: 10.1242/jcs.100.1.1. [DOI] [PubMed] [Google Scholar]
  23. Johnson A. D. The price of repression. Cell. 1995 Jun 2;81(5):655–658. doi: 10.1016/0092-8674(95)90524-3. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Karch F., Galloni M., Sipos L., Gausz J., Gyurkovics H., Schedl P. Mcp and Fab-7: molecular analysis of putative boundaries of cis-regulatory domains in the bithorax complex of Drosophila melanogaster. Nucleic Acids Res. 1994 Aug 11;22(15):3138–3146. doi: 10.1093/nar/22.15.3138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Karch F., Weiffenbach B., Peifer M., Bender W., Duncan I., Celniker S., Crosby M., Lewis E. B. The abdominal region of the bithorax complex. Cell. 1985 Nov;43(1):81–96. doi: 10.1016/0092-8674(85)90014-5. [DOI] [PubMed] [Google Scholar]
  27. Kassis J. A., VanSickle E. P., Sensabaugh S. M. A fragment of engrailed regulatory DNA can mediate transvection of the white gene in Drosophila. Genetics. 1991 Aug;128(4):751–761. doi: 10.1093/genetics/128.4.751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kellum R., Schedl P. A position-effect assay for boundaries of higher order chromosomal domains. Cell. 1991 Mar 8;64(5):941–950. doi: 10.1016/0092-8674(91)90318-s. [DOI] [PubMed] [Google Scholar]
  29. Kennison J. A., Russell M. A. Dosage-Dependent Modifiers of Homoeotic Mutations in Drosophila melanogaster. Genetics. 1987 May;116(1):75–86. doi: 10.1093/genetics/116.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kennison J. A., Tamkun J. W. Dosage-dependent modifiers of polycomb and antennapedia mutations in Drosophila. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8136–8140. doi: 10.1073/pnas.85.21.8136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Laney J. D., Biggin M. D. zeste, a nonessential gene, potently activates Ultrabithorax transcription in the Drosophila embryo. Genes Dev. 1992 Aug;6(8):1531–1541. doi: 10.1101/gad.6.8.1531. [DOI] [PubMed] [Google Scholar]
  32. Laurenson P., Rine J. Silencers, silencing, and heritable transcriptional states. Microbiol Rev. 1992 Dec;56(4):543–560. doi: 10.1128/mr.56.4.543-560.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Levis R., Hazelrigg T., Rubin G. M. Separable cis-acting control elements for expression of the white gene of Drosophila. EMBO J. 1985 Dec 16;4(13A):3489–3499. doi: 10.1002/j.1460-2075.1985.tb04108.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lewis E. B. A gene complex controlling segmentation in Drosophila. Nature. 1978 Dec 7;276(5688):565–570. doi: 10.1038/276565a0. [DOI] [PubMed] [Google Scholar]
  35. Lu Q., Wallrath L. L., Granok H., Elgin S. C. (CT)n (GA)n repeats and heat shock elements have distinct roles in chromatin structure and transcriptional activation of the Drosophila hsp26 gene. Mol Cell Biol. 1993 May;13(5):2802–2814. doi: 10.1128/mcb.13.5.2802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Mihaly J., Hogga I., Gausz J., Gyurkovics H., Karch F. In situ dissection of the Fab-7 region of the bithorax complex into a chromatin domain boundary and a Polycomb-response element. Development. 1997 May;124(9):1809–1820. doi: 10.1242/dev.124.9.1809. [DOI] [PubMed] [Google Scholar]
  37. Moehrle A., Paro R. Spreading the silence: epigenetic transcriptional regulation during Drosophila development. Dev Genet. 1994;15(6):478–484. doi: 10.1002/dvg.1020150606. [DOI] [PubMed] [Google Scholar]
  38. Müller J., Bienz M. Long range repression conferring boundaries of Ultrabithorax expression in the Drosophila embryo. EMBO J. 1991 Nov;10(11):3147–3155. doi: 10.1002/j.1460-2075.1991.tb04876.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. O'Hare K., Murphy C., Levis R., Rubin G. M. DNA sequence of the white locus of Drosophila melanogaster. J Mol Biol. 1984 Dec 15;180(3):437–455. doi: 10.1016/0022-2836(84)90021-4. [DOI] [PubMed] [Google Scholar]
  40. Paro R. Imprinting a determined state into the chromatin of Drosophila. Trends Genet. 1990 Dec;6(12):416–421. doi: 10.1016/0168-9525(90)90303-n. [DOI] [PubMed] [Google Scholar]
  41. Pirrotta V., Steller H., Bozzetti M. P. Multiple upstream regulatory elements control the expression of the Drosophila white gene. EMBO J. 1985 Dec 16;4(13A):3501–3508. doi: 10.1002/j.1460-2075.1985.tb04109.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Pirrotta V. The genetics and molecular biology of zeste in Drosophila melanogaster. Adv Genet. 1991;29:301–348. doi: 10.1016/s0065-2660(08)60110-8. [DOI] [PubMed] [Google Scholar]
  43. Poux S., Kostic C., Pirrotta V. Hunchback-independent silencing of late Ubx enhancers by a Polycomb Group Response Element. EMBO J. 1996 Sep 2;15(17):4713–4722. [PMC free article] [PubMed] [Google Scholar]
  44. Reuter G., Spierer P. Position effect variegation and chromatin proteins. Bioessays. 1992 Sep;14(9):605–612. doi: 10.1002/bies.950140907. [DOI] [PubMed] [Google Scholar]
  45. Simon J., Chiang A., Bender W., Shimell M. J., O'Connor M. Elements of the Drosophila bithorax complex that mediate repression by Polycomb group products. Dev Biol. 1993 Jul;158(1):131–144. doi: 10.1006/dbio.1993.1174. [DOI] [PubMed] [Google Scholar]
  46. Simon J. Locking in stable states of gene expression: transcriptional control during Drosophila development. Curr Opin Cell Biol. 1995 Jun;7(3):376–385. doi: 10.1016/0955-0674(95)80093-x. [DOI] [PubMed] [Google Scholar]
  47. Simon J., Peifer M., Bender W., O'Connor M. Regulatory elements of the bithorax complex that control expression along the anterior-posterior axis. EMBO J. 1990 Dec;9(12):3945–3956. doi: 10.1002/j.1460-2075.1990.tb07615.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Soeller W. C., Oh C. E., Kornberg T. B. Isolation of cDNAs encoding the Drosophila GAGA transcription factor. Mol Cell Biol. 1993 Dec;13(12):7961–7970. doi: 10.1128/mcb.13.12.7961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Tartof K. D., Henikoff S. Trans-sensing effects from Drosophila to humans. Cell. 1991 Apr 19;65(2):201–203. doi: 10.1016/0092-8674(91)90153-p. [DOI] [PubMed] [Google Scholar]
  50. Tsukiyama T., Becker P. B., Wu C. ATP-dependent nucleosome disruption at a heat-shock promoter mediated by binding of GAGA transcription factor. Nature. 1994 Feb 10;367(6463):525–532. doi: 10.1038/367525a0. [DOI] [PubMed] [Google Scholar]
  51. Vazquez J., Farkas G., Gaszner M., Udvardy A., Muller M., Hagstrom K., Gyurkovics H., Sipos L., Gausz J., Galloni M. Genetic and molecular analysis of chromatin domains. Cold Spring Harb Symp Quant Biol. 1993;58:45–54. doi: 10.1101/sqb.1993.058.01.008. [DOI] [PubMed] [Google Scholar]
  52. Vazquez J., Schedl P. Sequences required for enhancer blocking activity of scs are located within two nuclease-hypersensitive regions. EMBO J. 1994 Dec 15;13(24):5984–5993. doi: 10.1002/j.1460-2075.1994.tb06944.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. White R. A., Lehmann R. A gap gene, hunchback, regulates the spatial expression of Ultrabithorax. Cell. 1986 Oct 24;47(2):311–321. doi: 10.1016/0092-8674(86)90453-8. [DOI] [PubMed] [Google Scholar]
  54. Wu C. T. Transvection, nuclear structure, and chromatin proteins. J Cell Biol. 1993 Feb;120(3):587–590. doi: 10.1083/jcb.120.3.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Zhou J., Barolo S., Szymanski P., Levine M. The Fab-7 element of the bithorax complex attenuates enhancer-promoter interactions in the Drosophila embryo. Genes Dev. 1996 Dec 15;10(24):3195–3201. doi: 10.1101/gad.10.24.3195. [DOI] [PubMed] [Google Scholar]
  56. Zink D., Paro R. Drosophila Polycomb-group regulated chromatin inhibits the accessibility of a trans-activator to its target DNA. EMBO J. 1995 Nov 15;14(22):5660–5671. doi: 10.1002/j.1460-2075.1995.tb00253.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES