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. 1994 Dec 15;13(24):5977–5983. doi: 10.1002/j.1460-2075.1994.tb06943.x

The Drosophila GAGA transcription factor is associated with specific regions of heterochromatin throughout the cell cycle.

J W Raff 1, R Kellum 1, B Alberts 1
PMCID: PMC395573  PMID: 7813435

Abstract

In virtually all eukaryotes the centromeric regions of chromosomes are composed of heterochromatin, a specialized form of chromatin that is rich in repetitive DNA sequences and is transcriptionally relatively silent. The Drosophila GAGA transcription factor binds to GA/CT-rich sequences in many Drosophila promoters, where it activates transcription, apparently by locally altering chromatin structure and allowing other transcription factors access to the DNA. Here we report the paradoxical finding that GAGA factor is associated with specific regions of heterochromatin at all stages of the cell cycle. A subset of the highly repetitive DNA sequences that make up the bulk of heterochromatin in D. melanogaster are GA/CT-rich and we find a striking correlation between the distribution of GAGA factor and this class of repeat. We propose that GAGA factor binds directly to these repeats and may thereby play a role in modifying heterochromatin structure in these regions. Our observations demonstrate for the first time that a transcriptional regulator can associate with specific DNA sequences in a fully condensed mitotic chromosome. This may help explain how the distinctive character of a committed or differentiated cell can be maintained during cell proliferation.

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Selected References

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

  1. Bienz M. Molecular mechanisms of determination in Drosophila. Curr Opin Cell Biol. 1992 Dec;4(6):955–961. doi: 10.1016/0955-0674(92)90124-u. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Brutlag D. L. Molecular arrangement and evolution of heterochromatic DNA. Annu Rev Genet. 1980;14:121–144. doi: 10.1146/annurev.ge.14.120180.001005. [DOI] [PubMed] [Google Scholar]
  4. DiBello P. R., Withers D. A., Bayer C. A., Fristrom J. W., Guild G. M. The Drosophila Broad-Complex encodes a family of related proteins containing zinc fingers. Genetics. 1991 Oct;129(2):385–397. doi: 10.1093/genetics/129.2.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dorer D. R., Henikoff S. Expansions of transgene repeats cause heterochromatin formation and gene silencing in Drosophila. Cell. 1994 Jul 1;77(7):993–1002. doi: 10.1016/0092-8674(94)90439-1. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Earnshaw W. C., Rothfield N. Identification of a family of human centromere proteins using autoimmune sera from patients with scleroderma. Chromosoma. 1985;91(3-4):313–321. doi: 10.1007/BF00328227. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Felsenfeld G. Chromatin as an essential part of the transcriptional mechanism. Nature. 1992 Jan 16;355(6357):219–224. doi: 10.1038/355219a0. [DOI] [PubMed] [Google Scholar]
  11. Gall J. G., Atherton D. D. Satellite DNA sequences in Drosophila virilis. J Mol Biol. 1974 Jan 5;85(4):633–664. doi: 10.1016/0022-2836(74)90321-0. [DOI] [PubMed] [Google Scholar]
  12. Gall J. G., Cohen E. H., Polan M. L. Reptitive DNA sequences in drosophila. Chromosoma. 1971;33(3):319–344. doi: 10.1007/BF00284948. [DOI] [PubMed] [Google Scholar]
  13. Garzino V., Pereira A., Laurenti P., Graba Y., Levis R. W., Le Parco Y., Pradel J. Cell lineage-specific expression of modulo, a dose-dependent modifier of variegation in Drosophila. EMBO J. 1992 Dec;11(12):4471–4479. doi: 10.1002/j.1460-2075.1992.tb05548.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gatti M., Pimpinelli S. Functional elements in Drosophila melanogaster heterochromatin. Annu Rev Genet. 1992;26:239–275. doi: 10.1146/annurev.ge.26.120192.001323. [DOI] [PubMed] [Google Scholar]
  15. Grigliatti T. Position-effect variegation--an assay for nonhistone chromosomal proteins and chromatin assembly and modifying factors. Methods Cell Biol. 1991;35:587–627. [PubMed] [Google Scholar]
  16. Grunstein M. Nucleosomes: regulators of transcription. Trends Genet. 1990 Dec;6(12):395–400. doi: 10.1016/0168-9525(90)90299-l. [DOI] [PubMed] [Google Scholar]
  17. Harrison S. D., Travers A. A. The tramtrack gene encodes a Drosophila finger protein that interacts with the ftz transcriptional regulatory region and shows a novel embryonic expression pattern. EMBO J. 1990 Jan;9(1):207–216. doi: 10.1002/j.1460-2075.1990.tb08097.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Henikoff S. Position effect and related phenomena. Curr Opin Genet Dev. 1992 Dec;2(6):907–912. doi: 10.1016/s0959-437x(05)80114-5. [DOI] [PubMed] [Google Scholar]
  19. Hilliker A. J., Appels R., Schalet A. The genetic analysis of D. melanogaster heterochromatin. Cell. 1980 Oct;21(3):607–619. doi: 10.1016/0092-8674(80)90424-9. [DOI] [PubMed] [Google Scholar]
  20. Hiraoka Y., Agard D. A., Sedat J. W. Temporal and spatial coordination of chromosome movement, spindle formation, and nuclear envelope breakdown during prometaphase in Drosophila melanogaster embryos. J Cell Biol. 1990 Dec;111(6 Pt 2):2815–2828. doi: 10.1083/jcb.111.6.2815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. James T. C., Elgin S. C. Identification of a nonhistone chromosomal protein associated with heterochromatin in Drosophila melanogaster and its gene. Mol Cell Biol. 1986 Nov;6(11):3862–3872. doi: 10.1128/mcb.6.11.3862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Karpen G. H. Position-effect variegation and the new biology of heterochromatin. Curr Opin Genet Dev. 1994 Apr;4(2):281–291. doi: 10.1016/s0959-437x(05)80055-3. [DOI] [PubMed] [Google Scholar]
  23. Kellogg D. R., Alberts B. M. Purification of a multiprotein complex containing centrosomal proteins from the Drosophila embryo by chromatography with low-affinity polyclonal antibodies. Mol Biol Cell. 1992 Jan;3(1):1–11. doi: 10.1091/mbc.3.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Lohe A. R., Hilliker A. J., Roberts P. A. Mapping simple repeated DNA sequences in heterochromatin of Drosophila melanogaster. Genetics. 1993 Aug;134(4):1149–1174. doi: 10.1093/genetics/134.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Palmer D. K., O'Day K., Trong H. L., Charbonneau H., Margolis R. L. Purification of the centromere-specific protein CENP-A and demonstration that it is a distinctive histone. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3734–3738. doi: 10.1073/pnas.88.9.3734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Paro R. Imprinting a determined state into the chromatin of Drosophila. Trends Genet. 1990 Dec;6(12):416–421. doi: 10.1016/0168-9525(90)90303-n. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Raff J. W., Kellogg D. R., Alberts B. M. Drosophila gamma-tubulin is part of a complex containing two previously identified centrosomal MAPs. J Cell Biol. 1993 May;121(4):823–835. doi: 10.1083/jcb.121.4.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Reuter G., Giarre M., Farah J., Gausz J., Spierer A., Spierer P. Dependence of position-effect variegation in Drosophila on dose of a gene encoding an unusual zinc-finger protein. Nature. 1990 Mar 15;344(6263):219–223. doi: 10.1038/344219a0. [DOI] [PubMed] [Google Scholar]
  32. Reuter G., Spierer P. Position effect variegation and chromatin proteins. Bioessays. 1992 Sep;14(9):605–612. doi: 10.1002/bies.950140907. [DOI] [PubMed] [Google Scholar]
  33. Rudkin G. T. Non replicating DNA in Drosophila. Genetics. 1969;61(1 Suppl):227–238. [PubMed] [Google Scholar]
  34. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  35. Soeller W. C., Oh C. E., Kornberg T. B. Isolation of cDNAs encoding the Drosophila GAGA transcription factor. Mol Cell Biol. 1993 Dec;13(12):7961–7970. doi: 10.1128/mcb.13.12.7961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sullivan K. F., Glass C. A. CENP-B is a highly conserved mammalian centromere protein with homology to the helix-loop-helix family of proteins. Chromosoma. 1991 Jul;100(6):360–370. doi: 10.1007/BF00337514. [DOI] [PubMed] [Google Scholar]
  37. 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]

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