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. 1996 Nov;144(3):1143–1154. doi: 10.1093/genetics/144.3.1143

Genes Regulating the Remote Wing Margin Enhancer in the Drosophila Cut Locus

P Morcillo 1, C Rosen 1, D Dorsett 1
PMCID: PMC1207607  PMID: 8913756

Abstract

The mechanisms that allow enhancers to activate promoters from thousands of base pairs away are disrupted by the suppressor of Hairy-wing protein (SUHW) of Drosophila. SUHW binds a DNA sequence in the gypsy retrotransposon and prevents enhancers promoter-distal to a gypsy insertion in a gene from activating without affecting promoter-proximal enhancers. Several observations indicate that SUHW does not affect enhancer-binding activators. Instead, SUHW may interfere with factors that structurally facilitate interactions between an enhancer and promoter. To identify putative enhancer facilitators, a screen for mutations that reduce activity of the remote wing margin enhancer in the cut gene was performed. Mutations in scalloped, mastermind, and a previously unknown gene, Chip, were isolated. A TEA DNA-binding domain in the Scalloped protein binds the wing margin enhancer. Interactions between scalloped, mastermind and Chip mutations indicate that mastermind and Chip act synergistically with scalloped to regulate the wing margin enhancer. Chip is essential and also affects expression of a gypsy insertion in Ultrabithorax. Relative to mutations in scalloped or mastermind, a Chip mutation hypersensitizes the wing margin enhancer in cut to gypsy insertions. Therefore, Chip might encode a target of SUHW enhancer-blocking activity.

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Selected References

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

  1. Bettler D., Pearson S., Yedvobnick B. The nuclear protein encoded by the Drosophila neurogenic gene mastermind is widely expressed and associates with specific chromosomal regions. Genetics. 1996 Jun;143(2):859–875. doi: 10.1093/genetics/143.2.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bickel S., Pirrotta V. Self-association of the Drosophila zeste protein is responsible for transvection effects. EMBO J. 1990 Sep;9(9):2959–2967. doi: 10.1002/j.1460-2075.1990.tb07488.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blochlinger K., Bodmer R., Jack J., Jan L. Y., Jan Y. N. Primary structure and expression of a product from cut, a locus involved in specifying sensory organ identity in Drosophila. Nature. 1988 Jun 16;333(6174):629–635. doi: 10.1038/333629a0. [DOI] [PubMed] [Google Scholar]
  4. Buescher M. D., Rutledge L. C., Wirtz R. A., Glackin K. B., Moussa M. A. Laboratory tests of repellents against Lutzomyia longipalpis (Diptera: Psychodidae). J Med Entomol. 1982 Mar 24;19(2):176–180. doi: 10.1093/jmedent/19.2.176. [DOI] [PubMed] [Google Scholar]
  5. Bürglin T. R. The TEA domain: a novel, highly conserved DNA-binding motif. Cell. 1991 Jul 12;66(1):11–12. doi: 10.1016/0092-8674(91)90132-i. [DOI] [PubMed] [Google Scholar]
  6. Cai H., Levine M. Modulation of enhancer-promoter interactions by insulators in the Drosophila embryo. Nature. 1995 Aug 10;376(6540):533–536. doi: 10.1038/376533a0. [DOI] [PubMed] [Google Scholar]
  7. Davidson I., Xiao J. H., Rosales R., Staub A., Chambon P. The HeLa cell protein TEF-1 binds specifically and cooperatively to two SV40 enhancer motifs of unrelated sequence. Cell. 1988 Sep 23;54(7):931–942. doi: 10.1016/0092-8674(88)90108-0. [DOI] [PubMed] [Google Scholar]
  8. Dorn R., Krauss V., Reuter G., Saumweber H. The enhancer of position-effect variegation of Drosophila, E(var)3-93D, codes for a chromatin protein containing a conserved domain common to several transcriptional regulators. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11376–11380. doi: 10.1073/pnas.90.23.11376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dorsett D. Distance-independent inactivation of an enhancer by the suppressor of Hairy-wing DNA-binding protein of Drosophila. Genetics. 1993 Aug;134(4):1135–1144. doi: 10.1093/genetics/134.4.1135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dunn T. M., Hahn S., Ogden S., Schleif R. F. An operator at -280 base pairs that is required for repression of araBAD operon promoter: addition of DNA helical turns between the operator and promoter cyclically hinders repression. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5017–5020. doi: 10.1073/pnas.81.16.5017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fischer J. A., Giniger E., Maniatis T., Ptashne M. GAL4 activates transcription in Drosophila. Nature. 1988 Apr 28;332(6167):853–856. doi: 10.1038/332853a0. [DOI] [PubMed] [Google Scholar]
  12. Fromental C., Kanno M., Nomiyama H., Chambon P. Cooperativity and hierarchical levels of functional organization in the SV40 enhancer. Cell. 1988 Sep 23;54(7):943–953. doi: 10.1016/0092-8674(88)90109-2. [DOI] [PubMed] [Google Scholar]
  13. Georgiev P. G., Corces V. G. The su(Hw) protein bound to gypsy sequences in one chromosome can repress enhancer-promoter interactions in the paired gene located in the other homolog. Proc Natl Acad Sci U S A. 1995 May 23;92(11):5184–5188. doi: 10.1073/pnas.92.11.5184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Georgiev P. G., Gerasimova T. I. Novel genes influencing the expression of the yellow locus and mdg4 (gypsy) in Drosophila melanogaster. Mol Gen Genet. 1989 Dec;220(1):121–126. doi: 10.1007/BF00260865. [DOI] [PubMed] [Google Scholar]
  15. Georgiev P., Kozycina M. Interaction between mutations in the suppressor of Hairy wing and modifier of mdg4 genes of Drosophila melanogaster affecting the phenotype of gypsy-induced mutations. Genetics. 1996 Feb;142(2):425–436. doi: 10.1093/genetics/142.2.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gerasimova T. I., Gdula D. A., Gerasimov D. V., Simonova O., Corces V. G. A Drosophila protein that imparts directionality on a chromatin insulator is an enhancer of position-effect variegation. Cell. 1995 Aug 25;82(4):587–597. doi: 10.1016/0092-8674(95)90031-4. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Griffith J., Hochschild A., Ptashne M. DNA loops induced by cooperative binding of lambda repressor. Nature. 1986 Aug 21;322(6081):750–752. doi: 10.1038/322750a0. [DOI] [PubMed] [Google Scholar]
  19. Harrison D. A., Gdula D. A., Coyne R. S., Corces V. G. A leucine zipper domain of the suppressor of Hairy-wing protein mediates its repressive effect on enhancer function. Genes Dev. 1993 Oct;7(10):1966–1978. doi: 10.1101/gad.7.10.1966. [DOI] [PubMed] [Google Scholar]
  20. Holdridge C., Dorsett D. Repression of hsp70 heat shock gene transcription by the suppressor of hairy-wing protein of Drosophila melanogaster. Mol Cell Biol. 1991 Apr;11(4):1894–1900. doi: 10.1128/mcb.11.4.1894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jack J., DeLotto Y. Effect of wing scalloping mutations on cut expression and sense organ differentiation in the Drosophila wing margin. Genetics. 1992 Jun;131(2):353–363. doi: 10.1093/genetics/131.2.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jack J., DeLotto Y. Structure and regulation of a complex locus: the cut gene of Drosophila. Genetics. 1995 Apr;139(4):1689–1700. doi: 10.1093/genetics/139.4.1689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kakidani H., Ptashne M. GAL4 activates gene expression in mammalian cells. Cell. 1988 Jan 29;52(2):161–167. doi: 10.1016/0092-8674(88)90504-1. [DOI] [PubMed] [Google Scholar]
  24. Kim J., Shen B., Dorsett D. The Drosophila melanogaster suppressor of Hairy-wing zinc finger protein has minimal effects on gene expression in Saccharomyces cerevisiae. Genetics. 1993 Oct;135(2):343–355. doi: 10.1093/genetics/135.2.343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kim J., Shen B., Rosen C., Dorsett D. The DNA-binding and enhancer-blocking domains of the Drosophila suppressor of Hairy-wing protein. Mol Cell Biol. 1996 Jul;16(7):3381–3392. doi: 10.1128/mcb.16.7.3381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Künzler M., Braus G. H., Georgiev O., Seipel K., Schaffner W. Functional differences between mammalian transcription activation domains at the yeast GAL1 promoter. EMBO J. 1994 Feb 1;13(3):641–645. doi: 10.1002/j.1460-2075.1994.tb06302.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Metzger D., White J. H., Chambon P. The human oestrogen receptor functions in yeast. Nature. 1988 Jul 7;334(6177):31–36. doi: 10.1038/334031a0. [DOI] [PubMed] [Google Scholar]
  28. Mogila V. A., Ladvishenko A. B., Simonova O. B., Gerasimova T. I. Intragenic suppression: Stalker, a retrovirus-like transposable element, can compensate for a deficiency at the cut locus of Drosophila melanogaster. Genetica. 1992;86(1-3):305–311. doi: 10.1007/BF00133729. [DOI] [PubMed] [Google Scholar]
  29. Peifer M., Bender W. The anterobithorax and bithorax mutations of the bithorax complex. EMBO J. 1986 Sep;5(9):2293–2303. doi: 10.1002/j.1460-2075.1986.tb04497.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Ptashne M. Gene regulation by proteins acting nearby and at a distance. Nature. 1986 Aug 21;322(6081):697–701. doi: 10.1038/322697a0. [DOI] [PubMed] [Google Scholar]
  32. Rutledge B. J., Mortin M. A., Schwarz E., Thierry-Mieg D., Meselson M. Genetic interactions of modifier genes and modifiable alleles in Drosophila melanogaster. Genetics. 1988 Jun;119(2):391–397. doi: 10.1093/genetics/119.2.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schena M., Yamamoto K. R. Mammalian glucocorticoid receptor derivatives enhance transcription in yeast. Science. 1988 Aug 19;241(4868):965–967. doi: 10.1126/science.3043665. [DOI] [PubMed] [Google Scholar]
  34. Scott K. S., Geyer P. K. Effects of the su(Hw) insulator protein on the expression of the divergently transcribed Drosophila yolk protein genes. EMBO J. 1995 Dec 15;14(24):6258–6267. doi: 10.1002/j.1460-2075.1995.tb00316.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Shen B., Kim J., Dorsett D. The enhancer-blocking suppressor of Hairy-wing zinc finger protein of Drosophila melanogaster alters DNA structure. Mol Cell Biol. 1994 Sep;14(9):5645–5652. doi: 10.1128/mcb.14.9.5645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Simon M. A., Bowtell D. D., Dodson G. S., Laverty T. R., Rubin G. M. Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase. Cell. 1991 Nov 15;67(4):701–716. doi: 10.1016/0092-8674(91)90065-7. [DOI] [PubMed] [Google Scholar]
  37. Singson A., Leviten M. W., Bang A. G., Hua X. H., Posakony J. W. Direct downstream targets of proneural activators in the imaginal disc include genes involved in lateral inhibitory signaling. Genes Dev. 1994 Sep 1;8(17):2058–2071. doi: 10.1101/gad.8.17.2058. [DOI] [PubMed] [Google Scholar]
  38. Smoller D., Friedel C., Schmid A., Bettler D., Lam L., Yedvobnick B. The Drosophila neurogenic locus mastermind encodes a nuclear protein unusually rich in amino acid homopolymers. Genes Dev. 1990 Oct;4(10):1688–1700. doi: 10.1101/gad.4.10.1688. [DOI] [PubMed] [Google Scholar]
  39. Spana C., Corces V. G. DNA bending is a determinant of binding specificity for a Drosophila zinc finger protein. Genes Dev. 1990 Sep;4(9):1505–1515. doi: 10.1101/gad.4.9.1505. [DOI] [PubMed] [Google Scholar]
  40. Walter J., Biggin M. D. DNA binding specificity of two homeodomain proteins in vitro and in Drosophila embryos. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2680–2685. doi: 10.1073/pnas.93.7.2680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Webster N., Jin J. R., Green S., Hollis M., Chambon P. The yeast UASG is a transcriptional enhancer in human HeLa cells in the presence of the GAL4 trans-activator. Cell. 1988 Jan 29;52(2):169–178. doi: 10.1016/0092-8674(88)90505-3. [DOI] [PubMed] [Google Scholar]
  42. Wu C. T., Goldberg M. L. The Drosophila zeste gene and transvection. Trends Genet. 1989 Jun;5(6):189–194. doi: 10.1016/0168-9525(89)90074-7. [DOI] [PubMed] [Google Scholar]
  43. Xiao J. H., Davidson I., Matthes H., Garnier J. M., Chambon P. Cloning, expression, and transcriptional properties of the human enhancer factor TEF-1. Cell. 1991 May 17;65(4):551–568. doi: 10.1016/0092-8674(91)90088-g. [DOI] [PubMed] [Google Scholar]
  44. Xu T., Rebay I., Fleming R. J., Scottgale T. N., Artavanis-Tsakonas S. The Notch locus and the genetic circuitry involved in early Drosophila neurogenesis. Genes Dev. 1990 Mar;4(3):464–475. doi: 10.1101/gad.4.3.464. [DOI] [PubMed] [Google Scholar]

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