Abstract
Polycomb response elements (PREs) can establish a silenced state that affects the expression of genes over considerable distances. We have tested the ability of insulator or boundary elements to block the repression of the miniwhite gene by the Ubx PRE. The gypsy element and the scs element interposed between PRE and miniwhite gene protect it against silencing but the scs' is only weakly effective. When the PRE-miniwhite gene construct is insulated from flanking chromosomal sequences by gypsy elements at both ends, it can still establish efficient silencing in some lines but not others. We show that this can be caused by interactions in trans with PREs at other sites. PRE-containing transposons inserted at different sites or even on different chromosomes can interact, resulting in enhanced silencing. These trans interactions are not blocked by the gypsy insulator and reveal the importance of nonhomologous associations between different regions of the genome for both silencing and activation of genes. The similarity between the behavior of PREs and enhancers suggests a model for their long-distance action.
Full Text
The Full Text of this article is available as a PDF (7.8 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boscheron C., Maillet L., Marcand S., Tsai-Pflugfelder M., Gasser S. M., Gilson E. Cooperation at a distance between silencers and proto-silencers at the yeast HML locus. EMBO J. 1996 May 1;15(9):2184–2195. [PMC free article] [PubMed] [Google Scholar]
- Csink A. K., Henikoff S. Genetic modification of heterochromatic association and nuclear organization in Drosophila. Nature. 1996 Jun 6;381(6582):529–531. doi: 10.1038/381529a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Farkas G., Udvardy A. Sequence of scs and scs' Drosophila DNA fragments with boundary function in the control of gene expression. Nucleic Acids Res. 1992 May 25;20(10):2604–2604. doi: 10.1093/nar/20.10.2604. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Geyer P. K., Corces V. G. DNA position-specific repression of transcription by a Drosophila zinc finger protein. Genes Dev. 1992 Oct;6(10):1865–1873. doi: 10.1101/gad.6.10.1865. [DOI] [PubMed] [Google Scholar]
- Geyer P. K., Spana C., Corces V. G. On the molecular mechanism of gypsy-induced mutations at the yellow locus of Drosophila melanogaster. EMBO J. 1986 Oct;5(10):2657–2662. doi: 10.1002/j.1460-2075.1986.tb04548.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Jack J., Dorsett D., Delotto Y., Liu S. Expression of the cut locus in the Drosophila wing margin is required for cell type specification and is regulated by a distant enhancer. Development. 1991 Nov;113(3):735–747. doi: 10.1242/dev.113.3.735. [DOI] [PubMed] [Google Scholar]
- Kapoun A. M., Kaufman T. C. Regulatory regions of the homeotic gene proboscipedia are sensitive to chromosomal pairing. Genetics. 1995 Jun;140(2):643–658. doi: 10.1093/genetics/140.2.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kassis J. A., VanSickle E. P., Sensabaugh S. M. A fragment of engrailed regulatory DNA can mediate transvection of the white gene in Drosophila. Genetics. 1991 Aug;128(4):751–761. doi: 10.1093/genetics/128.4.751. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kellum R., Schedl P. A group of scs elements function as domain boundaries in an enhancer-blocking assay. Mol Cell Biol. 1992 May;12(5):2424–2431. doi: 10.1128/mcb.12.5.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kellum R., Schedl P. A position-effect assay for boundaries of higher order chromosomal domains. Cell. 1991 Mar 8;64(5):941–950. doi: 10.1016/0092-8674(91)90318-s. [DOI] [PubMed] [Google Scholar]
- 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]
- Mazo A. M., Mizrokhi L. J., Karavanov A. A., Sedkov Y. A., Krichevskaja A. A., Ilyin Y. V. Suppression in Drosophila: su(Hw) and su(f) gene products interact with a region of gypsy (mdg4) regulating its transcriptional activity. EMBO J. 1989 Mar;8(3):903–911. doi: 10.1002/j.1460-2075.1989.tb03451.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Messmer S., Franke A., Paro R. Analysis of the functional role of the Polycomb chromo domain in Drosophila melanogaster. Genes Dev. 1992 Jul;6(7):1241–1254. doi: 10.1101/gad.6.7.1241. [DOI] [PubMed] [Google Scholar]
- Orlando V., Paro R. Mapping Polycomb-repressed domains in the bithorax complex using in vivo formaldehyde cross-linked chromatin. Cell. 1993 Dec 17;75(6):1187–1198. doi: 10.1016/0092-8674(93)90328-n. [DOI] [PubMed] [Google Scholar]
- 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]
- Pirrotta V. Chromatin complexes regulating gene expression in Drosophila. Curr Opin Genet Dev. 1995 Aug;5(4):466–472. doi: 10.1016/0959-437x(95)90050-q. [DOI] [PubMed] [Google Scholar]
- Pirrotta V., Rastelli L. White gene expression, repressive chromatin domains and homeotic gene regulation in Drosophila. Bioessays. 1994 Aug;16(8):549–556. doi: 10.1002/bies.950160808. [DOI] [PubMed] [Google Scholar]
- Pirrotta V. Vectors for P-mediated transformation in Drosophila. Biotechnology. 1988;10:437–456. doi: 10.1016/b978-0-409-90042-2.50028-3. [DOI] [PubMed] [Google Scholar]
- Poux S., Kostic C., Pirrotta V. Hunchback-independent silencing of late Ubx enhancers by a Polycomb Group Response Element. EMBO J. 1996 Sep 2;15(17):4713–4722. [PMC free article] [PubMed] [Google Scholar]
- Roseman R. R., Pirrotta V., Geyer P. K. The su(Hw) protein insulates expression of the Drosophila melanogaster white gene from chromosomal position-effects. EMBO J. 1993 Feb;12(2):435–442. doi: 10.1002/j.1460-2075.1993.tb05675.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rubin G. M., Spradling A. C. Vectors for P element-mediated gene transfer in Drosophila. Nucleic Acids Res. 1983 Sep 24;11(18):6341–6351. doi: 10.1093/nar/11.18.6341. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Vazquez J., Farkas G., Gaszner M., Udvardy A., Muller M., Hagstrom K., Gyurkovics H., Sipos L., Gausz J., Galloni M. Genetic and molecular analysis of chromatin domains. Cold Spring Harb Symp Quant Biol. 1993;58:45–54. doi: 10.1101/sqb.1993.058.01.008. [DOI] [PubMed] [Google Scholar]
- Vazquez J., Schedl P. Sequences required for enhancer blocking activity of scs are located within two nuclease-hypersensitive regions. EMBO J. 1994 Dec 15;13(24):5984–5993. doi: 10.1002/j.1460-2075.1994.tb06944.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walter J., Dever C. A., Biggin M. D. Two homeo domain proteins bind with similar specificity to a wide range of DNA sites in Drosophila embryos. Genes Dev. 1994 Jul 15;8(14):1678–1692. doi: 10.1101/gad.8.14.1678. [DOI] [PubMed] [Google Scholar]
- Wijgerde M., Grosveld F., Fraser P. Transcription complex stability and chromatin dynamics in vivo. Nature. 1995 Sep 21;377(6546):209–213. doi: 10.1038/377209a0. [DOI] [PubMed] [Google Scholar]
- Zhao K., Hart C. M., Laemmli U. K. Visualization of chromosomal domains with boundary element-associated factor BEAF-32. Cell. 1995 Jun 16;81(6):879–889. doi: 10.1016/0092-8674(95)90008-x. [DOI] [PubMed] [Google Scholar]
- Zink B., Engström Y., Gehring W. J., Paro R. Direct interaction of the Polycomb protein with Antennapedia regulatory sequences in polytene chromosomes of Drosophila melanogaster. EMBO J. 1991 Jan;10(1):153–162. doi: 10.1002/j.1460-2075.1991.tb07931.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zink D., Paro R. Drosophila Polycomb-group regulated chromatin inhibits the accessibility of a trans-activator to its target DNA. EMBO J. 1995 Nov 15;14(22):5660–5671. doi: 10.1002/j.1460-2075.1995.tb00253.x. [DOI] [PMC free article] [PubMed] [Google Scholar]