Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 2004 Jan;166(1):279–289. doi: 10.1534/genetics.166.1.279

The Drosophila GAGA factor is required for dosage compensation in males and for the formation of the male-specific-lethal complex chromatin entry site at 12DE.

Anthony J Greenberg 1, Judith L Yanowitz 1, Paul Schedl 1
PMCID: PMC1470682  PMID: 15020425

Abstract

Drosophila melanogaster males have one X chromosome, while females have two. To compensate for the resulting disparity in X-linked gene expression between the two sexes, most genes from the male X chromosome are hyperactivated by a special dosage compensation system. Dosage compensation is achieved by a complex of at least six proteins and two noncoding RNAs that specifically associate with the male X. A central question is how the X chromosome is recognized. According to a current model, complexes initially assemble at approximately 35 chromatin entry sites on the X and then spread bidirectionally along the chromosome where they occupy hundreds of sites. Here, we report that mutations in Trithorax-like (Trl) lead to the loss of a single chromatin entry site on the X, male lethality, and mislocalization of dosage compensation complexes.

Full Text

The Full Text of this article is available as a PDF (432.9 KB).

Selected References

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

  1. Baker B. S., Gorman M., Marín I. Dosage compensation in Drosophila. Annu Rev Genet. 1994;28:491–521. doi: 10.1146/annurev.ge.28.120194.002423. [DOI] [PubMed] [Google Scholar]
  2. Bashaw G. J., Baker B. S. The regulation of the Drosophila msl-2 gene reveals a function for Sex-lethal in translational control. Cell. 1997 May 30;89(5):789–798. doi: 10.1016/s0092-8674(00)80262-7. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Bone J. R., Lavender J., Richman R., Palmer M. J., Turner B. M., Kuroda M. I. Acetylated histone H4 on the male X chromosome is associated with dosage compensation in Drosophila. Genes Dev. 1994 Jan;8(1):96–104. doi: 10.1101/gad.8.1.96. [DOI] [PubMed] [Google Scholar]
  6. Cline T. W., Meyer B. J. Vive la différence: males vs females in flies vs worms. Annu Rev Genet. 1996;30:637–702. doi: 10.1146/annurev.genet.30.1.637. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Deshpande G., Samuels M. E., Schedl P. D. Sex-lethal interacts with splicing factors in vitro and in vivo. Mol Cell Biol. 1996 Sep;16(9):5036–5047. doi: 10.1128/mcb.16.9.5036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Deshpande G., Stukey J., Schedl P. scute (sis-b) function in Drosophila sex determination. Mol Cell Biol. 1995 Aug;15(8):4430–4440. doi: 10.1128/mcb.15.8.4430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Franke A., Baker B. S. The rox1 and rox2 RNAs are essential components of the compensasome, which mediates dosage compensation in Drosophila. Mol Cell. 1999 Jul;4(1):117–122. doi: 10.1016/s1097-2765(00)80193-8. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Hilfiker A., Hilfiker-Kleiner D., Pannuti A., Lucchesi J. C. mof, a putative acetyl transferase gene related to the Tip60 and MOZ human genes and to the SAS genes of yeast, is required for dosage compensation in Drosophila. EMBO J. 1997 Apr 15;16(8):2054–2060. doi: 10.1093/emboj/16.8.2054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jin Y., Wang Y., Johansen J., Johansen K. M. JIL-1, a chromosomal kinase implicated in regulation of chromatin structure, associates with the male specific lethal (MSL) dosage compensation complex. J Cell Biol. 2000 May 29;149(5):1005–1010. doi: 10.1083/jcb.149.5.1005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jin Y., Wang Y., Walker D. L., Dong H., Conley C., Johansen J., Johansen K. M. JIL-1: a novel chromosomal tandem kinase implicated in transcriptional regulation in Drosophila. Mol Cell. 1999 Jul;4(1):129–135. doi: 10.1016/s1097-2765(00)80195-1. [DOI] [PubMed] [Google Scholar]
  16. Kageyama Y., Mengus G., Gilfillan G., Kennedy H. G., Stuckenholz C., Kelley R. L., Becker P. B., Kuroda M. I. Association and spreading of the Drosophila dosage compensation complex from a discrete roX1 chromatin entry site. EMBO J. 2001 May 1;20(9):2236–2245. doi: 10.1093/emboj/20.9.2236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kelley R. L., Meller V. H., Gordadze P. R., Roman G., Davis R. L., Kuroda M. I. Epigenetic spreading of the Drosophila dosage compensation complex from roX RNA genes into flanking chromatin. Cell. 1999 Aug 20;98(4):513–522. doi: 10.1016/s0092-8674(00)81979-0. [DOI] [PubMed] [Google Scholar]
  18. Kelley R. L., Solovyeva I., Lyman L. M., Richman R., Solovyev V., Kuroda M. I. Expression of msl-2 causes assembly of dosage compensation regulators on the X chromosomes and female lethality in Drosophila. Cell. 1995 Jun 16;81(6):867–877. doi: 10.1016/0092-8674(95)90007-1. [DOI] [PubMed] [Google Scholar]
  19. Kelley R. L., Wang J., Bell L., Kuroda M. I. Sex lethal controls dosage compensation in Drosophila by a non-splicing mechanism. Nature. 1997 May 8;387(6629):195–199. doi: 10.1038/387195a0. [DOI] [PubMed] [Google Scholar]
  20. Kerrigan L. A., Croston G. E., Lira L. M., Kadonaga J. T. Sequence-specific transcriptional antirepression of the Drosophila Krüppel gene by the GAGA factor. J Biol Chem. 1991 Jan 5;266(1):574–582. [PubMed] [Google Scholar]
  21. 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]
  22. Lucchesi J. C., Manning J. E. Gene dosage compensation in Drosophila melanogaster. Adv Genet. 1987;24:371–429. doi: 10.1016/s0065-2660(08)60013-9. [DOI] [PubMed] [Google Scholar]
  23. Lyman L. M., Copps K., Rastelli L., Kelley R. L., Kuroda M. I. Drosophila male-specific lethal-2 protein: structure/function analysis and dependence on MSL-1 for chromosome association. Genetics. 1997 Dec;147(4):1743–1753. doi: 10.1093/genetics/147.4.1743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Meller V. H., Gordadze P. R., Park Y., Chu X., Stuckenholz C., Kelley R. L., Kuroda M. I. Ordered assembly of roX RNAs into MSL complexes on the dosage-compensated X chromosome in Drosophila. Curr Biol. 2000 Feb 10;10(3):136–143. doi: 10.1016/s0960-9822(00)00311-0. [DOI] [PubMed] [Google Scholar]
  25. Oh Hyangyee, Park Yongkyu, Kuroda Mitzi I. Local spreading of MSL complexes from roX genes on the Drosophila X chromosome. Genes Dev. 2003 Jun 1;17(11):1334–1339. doi: 10.1101/gad.1082003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Palmer M. J., Mergner V. A., Richman R., Manning J. E., Kuroda M. I., Lucchesi J. C. The male-specific lethal-one (msl-1) gene of Drosophila melanogaster encodes a novel protein that associates with the X chromosome in males. Genetics. 1993 Jun;134(2):545–557. doi: 10.1093/genetics/134.2.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Palmer M. J., Richman R., Richter L., Kuroda M. I. Sex-specific regulation of the male-specific lethal-1 dosage compensation gene in Drosophila. Genes Dev. 1994 Mar 15;8(6):698–706. doi: 10.1101/gad.8.6.698. [DOI] [PubMed] [Google Scholar]
  28. Pannuti A., Lucchesi J. C. Recycling to remodel: evolution of dosage-compensation complexes. Curr Opin Genet Dev. 2000 Dec;10(6):644–650. doi: 10.1016/s0959-437x(00)00136-2. [DOI] [PubMed] [Google Scholar]
  29. Park Yongkyu, Mengus Gabrielle, Bai Xiaoying, Kageyama Yuji, Meller Victoria H., Becker Peter B., Kuroda Mitzi I. Sequence-specific targeting of Drosophila roX genes by the MSL dosage compensation complex. Mol Cell. 2003 Apr;11(4):977–986. doi: 10.1016/s1097-2765(03)00147-3. [DOI] [PubMed] [Google Scholar]
  30. Parkhurst S. M., Ish-Horowicz D. wimp, a dominant maternal-effect mutation, reduces transcription of a specific subset of segmentation genes in Drosophila. Genes Dev. 1991 Mar;5(3):341–357. doi: 10.1101/gad.5.3.341. [DOI] [PubMed] [Google Scholar]
  31. Raff J. W., Kellum R., Alberts B. The Drosophila GAGA transcription factor is associated with specific regions of heterochromatin throughout the cell cycle. EMBO J. 1994 Dec 15;13(24):5977–5983. doi: 10.1002/j.1460-2075.1994.tb06943.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Zeidler M. P., Yokomori K., Tjian R., Mlodzik M. Drosophila TFIIA-S is up-regulated and required during Ras-mediated photoreceptor determination. Genes Dev. 1996 Jan 1;10(1):50–59. doi: 10.1101/gad.10.1.50. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES