Skip to main content
PMC home page
Genetics logoLink to Genetics
. 2004 Aug;167(4):1739–1747. doi: 10.1534/genetics.104.026955

Enhancer choice in cis and in trans in Drosophila melanogaster: role of the promoter.

James R Morris 1, Dmitri A Petrov 1, Anne M Lee 1, Chao-Ting Wu 1
PMCID: PMC1471007  PMID: 15342512

Abstract

Eukaryotic enhancers act over very long distances, yet still show remarkable specificity for their own promoter. To better understand mechanisms underlying this enhancer-promoter specificity, we used transvection to analyze enhancer choice between two promoters, one located in cis to the enhancer and the other in trans to the enhancer, at the yellow gene of Drosophila melanogaster. Previously, we demonstrated that enhancers at yellow prefer to act on the cis-linked promoter, but that mutation of core promoter elements in the cis-linked promoter releases enhancers to act in trans. Here, we address the mechanism by which these elements affect enhancer choice. We consider and explicitly test three models that are based on promoter competency, promoter pairing, and promoter identity. Through targeted gene replacement of the endogenous yellow gene, we show that competency of the cis-linked promoter is a key parameter in the cis-trans choice of an enhancer. In fact, complete replacement of the yellow promoter with both TATA-containing and TATA-less heterologous promoters maintains enhancer action in cis.

Full Text

The Full Text of this article is available as a PDF (144.0 KB).

Selected References

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

  1. Bean Christopher J., Schaner Christine E., Kelly William G. Meiotic pairing and imprinted X chromatin assembly in Caenorhabditis elegans. Nat Genet. 2003 Dec 21;36(1):100–105. doi: 10.1038/ng1283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Burgess Sean M. Homologous chromosome associations and nuclear order in meiotic and mitotically dividing cells of budding yeast. Adv Genet. 2002;46:49–90. doi: 10.1016/s0065-2660(02)46004-x. [DOI] [PubMed] [Google Scholar]
  3. Casares F., Bender W., Merriam J., Sánchez-Herrero E. Interactions of Drosophila Ultrabithorax regulatory regions with native and foreign promoters. Genetics. 1997 Jan;145(1):123–137. doi: 10.1093/genetics/145.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chen Ji-Long, Huisinga Kathryn L., Viering Michaela M., Ou Sharon A., Wu C-ting, Geyer Pamela K. Enhancer action in trans is permitted throughout the Drosophila genome. Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3723–3728. doi: 10.1073/pnas.062447999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Conte Caroline, Dastugue Bernard, Vaury Chantal. Promoter competition as a mechanism of transcriptional interference mediated by retrotransposons. EMBO J. 2002 Jul 15;21(14):3908–3916. doi: 10.1093/emboj/cdf367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dudley A. M., Gansheroff L. J., Winston F. Specific components of the SAGA complex are required for Gcn4- and Gcr1-mediated activation of the his4-912delta promoter in Saccharomyces cerevisiae. Genetics. 1999 Apr;151(4):1365–1378. doi: 10.1093/genetics/151.4.1365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Duncan Ian W. Transvection effects in Drosophila. Annu Rev Genet. 2002 Jun 11;36:521–556. doi: 10.1146/annurev.genet.36.060402.100441. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Gloor G. B., Nassif N. A., Johnson-Schlitz D. M., Preston C. R., Engels W. R. Targeted gene replacement in Drosophila via P element-induced gap repair. Science. 1991 Sep 6;253(5024):1110–1117. doi: 10.1126/science.1653452. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Golic M. M., Golic K. G. A quantitative measure of the mitotic pairing of alleles in Drosophila melanogaster and the influence of structural heterozygosity. Genetics. 1996 May;143(1):385–400. doi: 10.1093/genetics/143.1.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gubb D., Roote J., Trenear J., Coulson D., Ashburner M. Topological constraints on transvection between white genes within the transposing element TE35B in Drosophila melanogaster. Genetics. 1997 Jul;146(3):919–937. doi: 10.1093/genetics/146.3.919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hansen S. K., Tjian R. TAFs and TFIIA mediate differential utilization of the tandem Adh promoters. Cell. 1995 Aug 25;82(4):565–575. doi: 10.1016/0092-8674(95)90029-2. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Kadonaga James T. The DPE, a core promoter element for transcription by RNA polymerase II. Exp Mol Med. 2002 Sep 30;34(4):259–264. doi: 10.1038/emm.2002.36. [DOI] [PubMed] [Google Scholar]
  16. Kapoun A. M., Kaufman T. C. A functional analysis of 5', intronic and promoter regions of the homeotic gene proboscipedia in Drosophila melanogaster. Development. 1995 Jul;121(7):2127–2141. doi: 10.1242/dev.121.7.2127. [DOI] [PubMed] [Google Scholar]
  17. Keeler K. J., Dray T., Penney J. E., Gloor G. B. Gene targeting of a plasmid-borne sequence to a double-strand DNA break in Drosophila melanogaster. Mol Cell Biol. 1996 Feb;16(2):522–528. doi: 10.1128/mcb.16.2.522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kennison James A., Southworth Jeffrey W. Transvection in Drosophila. Adv Genet. 2002;46:399–420. doi: 10.1016/s0065-2660(02)46014-2. [DOI] [PubMed] [Google Scholar]
  19. Martin M., Meng Y. B., Chia W. Regulatory elements involved in the tissue-specific expression of the yellow gene of Drosophila. Mol Gen Genet. 1989 Jul;218(1):118–126. doi: 10.1007/BF00330574. [DOI] [PubMed] [Google Scholar]
  20. Martínez-Laborda A., González-Reyes A., Morata G. Trans regulation in the Ultrabithorax gene of Drosophila: alterations in the promoter enhance transvection. EMBO J. 1992 Oct;11(10):3645–3652. doi: 10.1002/j.1460-2075.1992.tb05449.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Merli C., Bergstrom D. E., Cygan J. A., Blackman R. K. Promoter specificity mediates the independent regulation of neighboring genes. Genes Dev. 1996 May 15;10(10):1260–1270. doi: 10.1101/gad.10.10.1260. [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. Morris J. R., Chen J., Filandrinos S. T., Dunn R. C., Fisk R., Geyer P. K., Wu C. An analysis of transvection at the yellow locus of Drosophila melanogaster. Genetics. 1999 Feb;151(2):633–651. doi: 10.1093/genetics/151.2.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Morris J. R., Geyer P. K., Wu C. T. Core promoter elements can regulate transcription on a separate chromosome in trans. Genes Dev. 1999 Feb 1;13(3):253–258. doi: 10.1101/gad.13.3.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Munte A., Aguade M., Segarra C. Changes in the recombinational environment affect divergence in the yellow gene of Drosophila. Mol Biol Evol. 2001 Jun;18(6):1045–1056. doi: 10.1093/oxfordjournals.molbev.a003876. [DOI] [PubMed] [Google Scholar]
  26. Munté A., Aguadé M., Segarra C. Nucleotide variation at the yellow gene region is not reduced in Drosophila subobscura: a study in relation to chromosomal polymorphism. Mol Biol Evol. 2000 Dec;17(12):1942–1955. doi: 10.1093/oxfordjournals.molbev.a026296. [DOI] [PubMed] [Google Scholar]
  27. Ohtsuki S., Levine M., Cai H. N. Different core promoters possess distinct regulatory activities in the Drosophila embryo. Genes Dev. 1998 Feb 15;12(4):547–556. doi: 10.1101/gad.12.4.547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Perisic O., Xiao H., Lis J. T. Stable binding of Drosophila heat shock factor to head-to-head and tail-to-tail repeats of a conserved 5 bp recognition unit. Cell. 1989 Dec 1;59(5):797–806. doi: 10.1016/0092-8674(89)90603-x. [DOI] [PubMed] [Google Scholar]
  29. Rubin G. M., Spradling A. C. Genetic transformation of Drosophila with transposable element vectors. Science. 1982 Oct 22;218(4570):348–353. doi: 10.1126/science.6289436. [DOI] [PubMed] [Google Scholar]
  30. Savitsky Mikhail, Kahn Tatyana, Pomerantseva Ekaterina, Georgiev Pavel. Transvection at the end of the truncated chromosome in Drosophila melanogaster. Genetics. 2003 Apr;163(4):1375–1387. doi: 10.1093/genetics/163.4.1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sharpe J., Nonchev S., Gould A., Whiting J., Krumlauf R. Selectivity, sharing and competitive interactions in the regulation of Hoxb genes. EMBO J. 1998 Mar 16;17(6):1788–1798. doi: 10.1093/emboj/17.6.1788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Smale Stephen T., Kadonaga James T. The RNA polymerase II core promoter. Annu Rev Biochem. 2003 Mar 19;72:449–479. doi: 10.1146/annurev.biochem.72.121801.161520. [DOI] [PubMed] [Google Scholar]
  34. Wittkopp Patricia J., Vaccaro Kathy, Carroll Sean B. Evolution of yellow gene regulation and pigmentation in Drosophila. Curr Biol. 2002 Sep 17;12(18):1547–1556. doi: 10.1016/s0960-9822(02)01113-2. [DOI] [PubMed] [Google Scholar]
  35. Wray Gregory A., Hahn Matthew W., Abouheif Ehab, Balhoff James P., Pizer Margaret, Rockman Matthew V., Romano Laura A. The evolution of transcriptional regulation in eukaryotes. Mol Biol Evol. 2003 May 30;20(9):1377–1419. doi: 10.1093/molbev/msg140. [DOI] [PubMed] [Google Scholar]
  36. Wu C. T., Morris J. R. Transvection and other homology effects. Curr Opin Genet Dev. 1999 Apr;9(2):237–246. doi: 10.1016/S0959-437X(99)80035-5. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES