Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 1999 Nov;153(3):1333–1356. doi: 10.1093/genetics/153.3.1333

The mcp element from the Drosophila melanogaster bithorax complex mediates long-distance regulatory interactions.

M Muller 1, K Hagstrom 1, H Gyurkovics 1, V Pirrotta 1, P Schedl 1
PMCID: PMC1460818  PMID: 10545463

Abstract

In the studies reported here, we have examined the properties of the Mcp element from the Drosophila melanogaster bithorax complex (BX-C). We have found that sequences from the Mcp region of BX-C have properties characteristic of Polycomb response elements (PREs), and that they silence adjacent reporters by a mechanism that requires trans-interactions between two copies of the transgene. However, Mcp trans-regulatory interactions have several novel features. In contrast to classical transvection, homolog pairing does not seem to be required. Thus, trans-regulatory interactions can be observed not only between Mcp transgenes inserted at the same site, but also between Mcp transgenes inserted at distant sites on the same chromosomal arm, or even on different arms. Trans-regulation can even be observed between transgenes inserted on different chromosomes. A small 800-bp Mcp sequence is sufficient to mediate these long-distance trans-regulatory interactions. This small fragment has little silencing activity on its own and must be combined with other Polycomb-Group-responsive elements to function as a "pairing-sensitive" silencer. Finally, this pairing element can also mediate long-distance interactions between enhancers and promoters, activating mini-white expression.

Full Text

The Full Text of this article is available as a PDF (753.0 KB).

Selected References

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

  1. Bornemann D., Miller E., Simon J. Expression and properties of wild-type and mutant forms of the Drosophila sex comb on midleg (SCM) repressor protein. Genetics. 1998 Oct;150(2):675–686. doi: 10.1093/genetics/150.2.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boulet A. M., Lloyd A., Sakonju S. Molecular definition of the morphogenetic and regulatory functions and the cis-regulatory elements of the Drosophila Abd-B homeotic gene. Development. 1991 Feb;111(2):393–405. doi: 10.1242/dev.111.2.393. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Brown J. L., Mucci D., Whiteley M., Dirksen M. L., Kassis J. A. The Drosophila Polycomb group gene pleiohomeotic encodes a DNA binding protein with homology to the transcription factor YY1. Mol Cell. 1998 Jun;1(7):1057–1064. doi: 10.1016/s1097-2765(00)80106-9. [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. Busturia A., Wightman C. D., Sakonju S. A silencer is required for maintenance of transcriptional repression throughout Drosophila development. Development. 1997 Nov;124(21):4343–4350. doi: 10.1242/dev.124.21.4343. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Celniker S. E., Sharma S., Keelan D. J., Lewis E. B. The molecular genetics of the bithorax complex of Drosophila: cis-regulation in the Abdominal-B domain. EMBO J. 1990 Dec;9(13):4277–4286. doi: 10.1002/j.1460-2075.1990.tb07876.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Chen J. D., Pirrotta V. Multimerization of the Drosophila zeste protein is required for efficient DNA binding. EMBO J. 1993 May;12(5):2075–2083. doi: 10.1002/j.1460-2075.1993.tb05856.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cheng N. N., Sinclair D. A., Campbell R. B., Brock H. W. Interactions of polyhomeotic with Polycomb group genes of Drosophila melanogaster. Genetics. 1994 Dec;138(4):1151–1162. doi: 10.1093/genetics/138.4.1151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Christen B., Bienz M. Imaginal disc silencers from Ultrabithorax: evidence for Polycomb response elements. Mech Dev. 1994 Dec;48(3):255–266. doi: 10.1016/0925-4773(94)90064-7. [DOI] [PubMed] [Google Scholar]
  14. Cumberledge S., Zaratzian A., Sakonju S. Characterization of two RNAs transcribed from the cis-regulatory region of the abd-A domain within the Drosophila bithorax complex. Proc Natl Acad Sci U S A. 1990 May;87(9):3259–3263. doi: 10.1073/pnas.87.9.3259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Duncan I. The bithorax complex. Annu Rev Genet. 1987;21:285–319. doi: 10.1146/annurev.ge.21.120187.001441. [DOI] [PubMed] [Google Scholar]
  18. Fung J. C., Marshall W. F., Dernburg A., Agard D. A., Sedat J. W. Homologous chromosome pairing in Drosophila melanogaster proceeds through multiple independent initiations. J Cell Biol. 1998 Apr 6;141(1):5–20. doi: 10.1083/jcb.141.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gelbart W. M. Synapsis-dependent allelic complementation at the decapentaplegic gene complex in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2636–2640. doi: 10.1073/pnas.79.8.2636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gemkow M. J., Verveer P. J., Arndt-Jovin D. J. Homologous association of the Bithorax-Complex during embryogenesis: consequences for transvection in Drosophila melanogaster. Development. 1998 Nov;125(22):4541–4552. doi: 10.1242/dev.125.22.4541. [DOI] [PubMed] [Google Scholar]
  21. Geyer P. K., Corces V. G. Separate regulatory elements are responsible for the complex pattern of tissue-specific and developmental transcription of the yellow locus in Drosophila melanogaster. Genes Dev. 1987 Nov;1(9):996–1004. doi: 10.1101/gad.1.9.996. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Goldsborough A. S., Kornberg T. B. Reduction of transcription by homologue asynapsis in Drosophila imaginal discs. Nature. 1996 Jun 27;381(6585):807–810. doi: 10.1038/381807a0. [DOI] [PubMed] [Google Scholar]
  24. Hagstrom K., Muller M., Schedl P. A Polycomb and GAGA dependent silencer adjoins the Fab-7 boundary in the Drosophila bithorax complex. Genetics. 1997 Aug;146(4):1365–1380. doi: 10.1093/genetics/146.4.1365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hagstrom K., Muller M., Schedl P. Fab-7 functions as a chromatin domain boundary to ensure proper segment specification by the Drosophila bithorax complex. Genes Dev. 1996 Dec 15;10(24):3202–3215. doi: 10.1101/gad.10.24.3202. [DOI] [PubMed] [Google Scholar]
  26. Hendrickson J. E., Sakonju S. Cis and trans interactions between the iab regulatory regions and abdominal-A and abdominal-B in Drosophila melanogaster. Genetics. 1995 Feb;139(2):835–848. doi: 10.1093/genetics/139.2.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Henikoff S., Dreesen T. D. Trans-inactivation of the Drosophila brown gene: evidence for transcriptional repression and somatic pairing dependence. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6704–6708. doi: 10.1073/pnas.86.17.6704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Henikoff S., Jackson J. M., Talbert P. B. Distance and pairing effects on the brownDominant heterochromatic element in Drosophila. Genetics. 1995 Jul;140(3):1007–1017. doi: 10.1093/genetics/140.3.1007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hiromi Y., Kuroiwa A., Gehring W. J. Control elements of the Drosophila segmentation gene fushi tarazu. Cell. 1985 Dec;43(3 Pt 2):603–613. doi: 10.1016/0092-8674(85)90232-6. [DOI] [PubMed] [Google Scholar]
  30. Hopmann R., Duncan D., Duncan I. Transvection in the iab-5,6,7 region of the bithorax complex of Drosophila: homology independent interactions in trans. Genetics. 1995 Feb;139(2):815–833. doi: 10.1093/genetics/139.2.815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Karch F., Bender W., Weiffenbach B. abdA expression in Drosophila embryos. Genes Dev. 1990 Sep;4(9):1573–1587. doi: 10.1101/gad.4.9.1573. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. 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]
  35. 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]
  36. 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]
  37. Lewis E. B. Regulation of the genes of the bithorax complex in Drosophila. Cold Spring Harb Symp Quant Biol. 1985;50:155–164. doi: 10.1101/sqb.1985.050.01.021. [DOI] [PubMed] [Google Scholar]
  38. Macias A., Casanova J., Morata G. Expression and regulation of the abd-A gene of Drosophila. Development. 1990 Dec;110(4):1197–1207. doi: 10.1242/dev.110.4.1197. [DOI] [PubMed] [Google Scholar]
  39. Mallin D. R., Myung J. S., Patton J. S., Geyer P. K. Polycomb group repression is blocked by the Drosophila suppressor of Hairy-wing [su(Hw)] insulator. Genetics. 1998 Jan;148(1):331–339. doi: 10.1093/genetics/148.1.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Marshall W. F., Straight A., Marko J. F., Swedlow J., Dernburg A., Belmont A., Murray A. W., Agard D. A., Sedat J. W. Interphase chromosomes undergo constrained diffusional motion in living cells. Curr Biol. 1997 Dec 1;7(12):930–939. doi: 10.1016/s0960-9822(06)00412-x. [DOI] [PubMed] [Google Scholar]
  41. Messmer S., Franke A., Paro R. Analysis of the functional role of the Polycomb chromo domain in Drosophila melanogaster. Genes Dev. 1992 Jul;6(7):1241–1254. doi: 10.1101/gad.6.7.1241. [DOI] [PubMed] [Google Scholar]
  42. Mihaly J., Hogga I., Barges S., Galloni M., Mishra R. K., Hagstrom K., Müller M., Schedl P., Sipos L., Gausz J. Chromatin domain boundaries in the Bithorax complex. Cell Mol Life Sci. 1998 Jan;54(1):60–70. doi: 10.1007/s000180050125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. 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]
  44. Mihaly J., Mishra R. K., Karch F. A conserved sequence motif in Polycomb-response elements. Mol Cell. 1998 Jun;1(7):1065–1066. doi: 10.1016/s1097-2765(00)80107-0. [DOI] [PubMed] [Google Scholar]
  45. Paro R. Mechanisms of heritable gene repression during development of Drosophila. Curr Opin Cell Biol. 1993 Dec;5(6):999–1005. doi: 10.1016/0955-0674(93)90084-4. [DOI] [PubMed] [Google Scholar]
  46. Pattatucci A. M., Kaufman T. C. The homeotic gene Sex combs reduced of Drosophila melanogaster is differentially regulated in the embryonic and imaginal stages of development. Genetics. 1991 Oct;129(2):443–461. doi: 10.1093/genetics/129.2.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Pirrotta V., Manet E., Hardon E., Bickel S. E., Benson M. Structure and sequence of the Drosophila zeste gene. EMBO J. 1987 Mar;6(3):791–799. doi: 10.1002/j.1460-2075.1987.tb04821.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Pirrotta V., Rastelli L. White gene expression, repressive chromatin domains and homeotic gene regulation in Drosophila. Bioessays. 1994 Aug;16(8):549–556. doi: 10.1002/bies.950160808. [DOI] [PubMed] [Google Scholar]
  49. Qian S., Pirrotta V. Dosage compensation of the Drosophila white gene requires both the X chromosome environment and multiple intragenic elements. Genetics. 1995 Feb;139(2):733–744. doi: 10.1093/genetics/139.2.733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. 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]
  51. 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]
  52. Simon J., Chiang A., Bender W. Ten different Polycomb group genes are required for spatial control of the abdA and AbdB homeotic products. Development. 1992 Feb;114(2):493–505. doi: 10.1242/dev.114.2.493. [DOI] [PubMed] [Google Scholar]
  53. Sipos L., Mihály J., Karch F., Schedl P., Gausz J., Gyurkovics H. Transvection in the Drosophila Abd-B domain: extensive upstream sequences are involved in anchoring distant cis-regulatory regions to the promoter. Genetics. 1998 Jun;149(2):1031–1050. doi: 10.1093/genetics/149.2.1031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Smolik-Utlaut S. M., Gelbart W. M. The effects of chromosomal rearrangements on the zeste-white interaction in Drosophila melanogaster. Genetics. 1987 Jun;116(2):285–298. doi: 10.1093/genetics/116.2.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Sánchez-Herrero E. Control of the expression of the bithorax complex genes abdominal-A and abdominal-B by cis-regulatory regions in Drosophila embryos. Development. 1991 Feb;111(2):437–449. doi: 10.1242/dev.111.2.437. [DOI] [PubMed] [Google Scholar]
  56. 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]
  57. 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]
  58. 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]
  59. 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]
  60. Wu C. T., Howe M. A genetic analysis of the Suppressor 2 of zeste complex of Drosophila melanogaster. Genetics. 1995 May;140(1):139–181. doi: 10.1093/genetics/140.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Wu C. T., Jones R. S., Lasko P. F., Gelbart W. M. Homeosis and the interaction of zeste and white in Drosophila. Mol Gen Genet. 1989 Sep;218(3):559–564. doi: 10.1007/BF00332424. [DOI] [PubMed] [Google Scholar]
  62. Zachar Z., Chapman C. H., Bingham P. M. On the molecular basis of transvection effects and the regulation of transcription. Cold Spring Harb Symp Quant Biol. 1985;50:337–346. doi: 10.1101/sqb.1985.050.01.043. [DOI] [PubMed] [Google Scholar]
  63. 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]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES