Skip to main content
PMC home page
Genetics logoLink to Genetics
. 2001 Jan;157(1):237–244. doi: 10.1093/genetics/157.1.237

DSP1, an HMG-like protein, is involved in the regulation of homeotic genes.

M Decoville 1, E Giacomello 1, M Leng 1, D Locker 1
PMCID: PMC1461500  PMID: 11139505

Abstract

The Drosophila dsp1 gene, which encodes an HMG-like protein, was originally identified in a screen for corepressors of Dorsal. Here we report that loss of dsp1 function causes homeotic transformations resembling those associated with loss of function in the homeotic genes Sex combs reduced (Scr), Ultrabithorax (Ubx), and Abdominal-B. The expression pattern of Scr is altered in dsp1 mutant imaginal discs, indicating that dsp1 is required for normal expression of this gene. Genetic interaction studies reveal that a null allele of dsp1 enhances trithorax-group gene (trx-G) mutations and partially suppresses Polycomb-group gene (Pc-G) mutations. On the contrary, overexpression of dsp1 induces an enhancement of the transformation of wings into halteres and of the extra sex comb phenotype of Pc. In addition, dsp1 male mutants exhibit a mild transformation of A4 into A5. Comparison of the chromatin structure at the Mcp locus in wild-type and dsp1 mutant embryos reveals that the 300-bp DNase I hypersensitive region is absent in a dsp1 mutant context. We propose that DSP1 protein is a chromatin remodeling factor, acting as a trx-G or a Pc-G protein depending on the considered function.

Full Text

The Full Text of this article is available as a PDF (285.6 KB).

Selected References

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

  1. Bonne-Andrea C., Harper F., Sobczak J., De Recondo A. M. Rat liver HMG1: a physiological nucleosome assembly factor. EMBO J. 1984 May;3(5):1193–1199. doi: 10.1002/j.1460-2075.1984.tb01950.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bonne C., Sautiere P., Duguet M., de Recondo A. M. Identification of a single-stranded DNA binding protein from rat liver with high mobility group protein 1. J Biol Chem. 1982 Mar 25;257(6):2722–2725. [PubMed] [Google Scholar]
  3. Breen T. R., Harte P. J. Molecular characterization of the trithorax gene, a positive regulator of homeotic gene expression in Drosophila. Mech Dev. 1991 Sep;35(2):113–127. doi: 10.1016/0925-4773(91)90062-b. [DOI] [PubMed] [Google Scholar]
  4. Cairns B. R., Lorch Y., Li Y., Zhang M., Lacomis L., Erdjument-Bromage H., Tempst P., Du J., Laurent B., Kornberg R. D. RSC, an essential, abundant chromatin-remodeling complex. Cell. 1996 Dec 27;87(7):1249–1260. doi: 10.1016/s0092-8674(00)81820-6. [DOI] [PubMed] [Google Scholar]
  5. Calogero S., Grassi F., Aguzzi A., Voigtländer T., Ferrier P., Ferrari S., Bianchi M. E. The lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice. Nat Genet. 1999 Jul;22(3):276–280. doi: 10.1038/10338. [DOI] [PubMed] [Google Scholar]
  6. Daubresse G., Deuring R., Moore L., Papoulas O., Zakrajsek I., Waldrip W. R., Scott M. P., Kennison J. A., Tamkun J. W. The Drosophila kismet gene is related to chromatin-remodeling factors and is required for both segmentation and segment identity. Development. 1999 Mar;126(6):1175–1187. doi: 10.1242/dev.126.6.1175. [DOI] [PubMed] [Google Scholar]
  7. Dingwall A. K., Beek S. J., McCallum C. M., Tamkun J. W., Kalpana G. V., Goff S. P., Scott M. P. The Drosophila snr1 and brm proteins are related to yeast SWI/SNF proteins and are components of a large protein complex. Mol Biol Cell. 1995 Jul;6(7):777–791. doi: 10.1091/mbc.6.7.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dorn R., Szidonya J., Korge G., Sehnert M., Taubert H., Archoukieh E., Tschiersch B., Morawietz H., Wustmann G., Hoffmann G. P transposon-induced dominant enhancer mutations of position-effect variegation in Drosophila melanogaster. Genetics. 1993 Feb;133(2):279–290. doi: 10.1093/genetics/133.2.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Duncan I. The bithorax complex. Annu Rev Genet. 1987;21:285–319. doi: 10.1146/annurev.ge.21.120187.001441. [DOI] [PubMed] [Google Scholar]
  10. Eissenberg J. C., James T. C., Foster-Hartnett D. M., Hartnett T., Ngan V., Elgin S. C. Mutation in a heterochromatin-specific chromosomal protein is associated with suppression of position-effect variegation in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9923–9927. doi: 10.1073/pnas.87.24.9923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Grosschedl R., Giese K., Pagel J. HMG domain proteins: architectural elements in the assembly of nucleoprotein structures. Trends Genet. 1994 Mar;10(3):94–100. doi: 10.1016/0168-9525(94)90232-1. [DOI] [PubMed] [Google Scholar]
  13. Ingham P. W. A clonal analysis of the requirement for the trithorax gene in the diversification of segments in Drosophila. J Embryol Exp Morphol. 1985 Oct;89:349–365. [PubMed] [Google Scholar]
  14. 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]
  15. Kaufman T. C., Seeger M. A., Olsen G. Molecular and genetic organization of the antennapedia gene complex of Drosophila melanogaster. Adv Genet. 1990;27:309–362. doi: 10.1016/s0065-2660(08)60029-2. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Lehming N., Le Saux A., Schüller J., Ptashne M. Chromatin components as part of a putative transcriptional repressing complex. Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7322–7326. doi: 10.1073/pnas.95.13.7322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lehming N., Thanos D., Brickman J. M., Ma J., Maniatis T., Ptashne M. An HMG-like protein that can switch a transcriptional activator to a repressor. Nature. 1994 Sep 8;371(6493):175–179. doi: 10.1038/371175a0. [DOI] [PubMed] [Google Scholar]
  19. Locke J., Kotarski M. A., Tartof K. D. Dosage-dependent modifiers of position effect variegation in Drosophila and a mass action model that explains their effect. Genetics. 1988 Sep;120(1):181–198. doi: 10.1093/genetics/120.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Masucci J. D., Miltenberger R. J., Hoffmann F. M. Pattern-specific expression of the Drosophila decapentaplegic gene in imaginal disks is regulated by 3' cis-regulatory elements. Genes Dev. 1990 Nov;4(11):2011–2023. doi: 10.1101/gad.4.11.2011. [DOI] [PubMed] [Google Scholar]
  21. Mosrin-Huaman C., Canaple L., Locker D., Decoville M. DSP1 gene of Drosophila melanogaster encodes an HMG-domain protein that plays multiple roles in development. Dev Genet. 1998;23(4):324–334. doi: 10.1002/(SICI)1520-6408(1998)23:4<324::AID-DVG7>3.0.CO;2-T. [DOI] [PubMed] [Google Scholar]
  22. Papoulas O., Beek S. J., Moseley S. L., McCallum C. M., Sarte M., Shearn A., Tamkun J. W. The Drosophila trithorax group proteins BRM, ASH1 and ASH2 are subunits of distinct protein complexes. Development. 1998 Oct;125(20):3955–3966. doi: 10.1242/dev.125.20.3955. [DOI] [PubMed] [Google Scholar]
  23. Paro R., Hogness D. S. The Polycomb protein shares a homologous domain with a heterochromatin-associated protein of Drosophila. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):263–267. doi: 10.1073/pnas.88.1.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pattatucci A. M., Otteson D. C., Kaufman T. C. A functional and structural analysis of the Sex combs reduced locus of Drosophila melanogaster. Genetics. 1991 Oct;129(2):423–441. doi: 10.1093/genetics/129.2.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rozovskaia T., Tillib S., Smith S., Sedkov Y., Rozenblatt-Rosen O., Petruk S., Yano T., Nakamura T., Ben-Simchon L., Gildea J. Trithorax and ASH1 interact directly and associate with the trithorax group-responsive bxd region of the Ultrabithorax promoter. Mol Cell Biol. 1999 Sep;19(9):6441–6447. doi: 10.1128/mcb.19.9.6441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Sinclair A. H., Berta P., Palmer M. S., Hawkins J. R., Griffiths B. L., Smith M. J., Foster J. W., Frischauf A. M., Lovell-Badge R., Goodfellow P. N. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature. 1990 Jul 19;346(6281):240–244. doi: 10.1038/346240a0. [DOI] [PubMed] [Google Scholar]
  29. Sinclair D. A., Clegg N. J., Antonchuk J., Milne T. A., Stankunas K., Ruse C., Grigliatti T. A., Kassis J. A., Brock H. W. Enhancer of Polycomb is a suppressor of position-effect variegation in Drosophila melanogaster. Genetics. 1998 Jan;148(1):211–220. doi: 10.1093/genetics/148.1.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sinclair D. A., Lloyd V. K., Grigliatti T. A. Characterization of mutations that enhance position-effect variegation in Drosophila melanogaster. Mol Gen Genet. 1989 Apr;216(2-3):328–333. doi: 10.1007/BF00334372. [DOI] [PubMed] [Google Scholar]
  31. Sinclair D. A., Milne T. A., Hodgson J. W., Shellard J., Salinas C. A., Kyba M., Randazzo F., Brock H. W. The Additional sex combs gene of Drosophila encodes a chromatin protein that binds to shared and unique Polycomb group sites on polytene chromosomes. Development. 1998 Apr;125(7):1207–1216. doi: 10.1242/dev.125.7.1207. [DOI] [PubMed] [Google Scholar]
  32. Sinclair D. A., Ruddell A. A., Brock J. K., Clegg N. J., Lloyd V. K., Grigliatti T. A. A cytogenetic and genetic characterization of a group of closely linked second chromosome mutations that suppress position-effect variegation in Drosophila melanogaster. Genetics. 1992 Feb;130(2):333–344. doi: 10.1093/genetics/130.2.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Singh J., Dixon G. H. High mobility group proteins 1 and 2 function as general class II transcription factors. Biochemistry. 1990 Jul 3;29(26):6295–6302. doi: 10.1021/bi00478a026. [DOI] [PubMed] [Google Scholar]
  34. Spradling A. C., Rubin G. M. Transposition of cloned P elements into Drosophila germ line chromosomes. Science. 1982 Oct 22;218(4570):341–347. doi: 10.1126/science.6289435. [DOI] [PubMed] [Google Scholar]
  35. Tautz D., Pfeifle C. A non-radioactive in situ hybridization method for the localization of specific RNAs in Drosophila embryos reveals translational control of the segmentation gene hunchback. Chromosoma. 1989 Aug;98(2):81–85. doi: 10.1007/BF00291041. [DOI] [PubMed] [Google Scholar]
  36. Travis A., Amsterdam A., Belanger C., Grosschedl R. LEF-1, a gene encoding a lymphoid-specific protein with an HMG domain, regulates T-cell receptor alpha enhancer function [corrected]. Genes Dev. 1991 May;5(5):880–894. doi: 10.1101/gad.5.5.880. [DOI] [PubMed] [Google Scholar]
  37. Tschiersch B., Hofmann A., Krauss V., Dorn R., Korge G., Reuter G. The protein encoded by the Drosophila position-effect variegation suppressor gene Su(var)3-9 combines domains of antagonistic regulators of homeotic gene complexes. EMBO J. 1994 Aug 15;13(16):3822–3831. doi: 10.1002/j.1460-2075.1994.tb06693.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wang W., Chi T., Xue Y., Zhou S., Kuo A., Crabtree G. R. Architectural DNA binding by a high-mobility-group/kinesin-like subunit in mammalian SWI/SNF-related complexes. Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):492–498. doi: 10.1073/pnas.95.2.492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Waterman M. L., Fischer W. H., Jones K. A. A thymus-specific member of the HMG protein family regulates the human T cell receptor C alpha enhancer. Genes Dev. 1991 Apr;5(4):656–669. doi: 10.1101/gad.5.4.656. [DOI] [PubMed] [Google Scholar]
  40. Wustmann G., Szidonya J., Taubert H., Reuter G. The genetics of position-effect variegation modifying loci in Drosophila melanogaster. Mol Gen Genet. 1989 Jun;217(2-3):520–527. doi: 10.1007/BF02464926. [DOI] [PubMed] [Google Scholar]
  41. Yamamoto Y., Girard F., Bello B., Affolter M., Gehring W. J. The cramped gene of Drosophila is a member of the Polycomb-group, and interacts with mus209, the gene encoding Proliferating Cell Nuclear Antigen. Development. 1997 Sep;124(17):3385–3394. doi: 10.1242/dev.124.17.3385. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES