A sequence motif found in a Drosophila heterochromatin protein is conserved in animals and plants (original) (raw)

Abstract

Modifiers of position-effect-variegation in Drosophila encode proteins that are thought to modify chromatin, rendering it heritably changed in its expressibility. In an attempt to identify similar modifier genes in other species we have utilized a known sequence homology, termed chromo box, between a suppressor of position-effect-variegation, Heterochromatin protein 1 (HP1), and a repressor of homeotic genes, Polycomb (Pc). A PCR generated probe encompassing the HP1 chromo box was used to clone full-length murine cDNAs that contain conserved chromo box motifs. Sequence comparisons, in situ hybridization experiments, and RNA Northern blot analysis suggest that the murine and human sequences presented in this report are homologues of the Drosophila HP1 gene. Chromo box sequences can also be detected in other animal species, and in plants, predicting a strongly conserved structural role for the peptide encoded by this sequence. We propose that epigenetic (yet heritable) changes in gene expressibility, characteristic of chromosomal imprinting phenomena, can largely be explained by the action of such modifier genes. The evolutionary conservation of the chromo box motif now enables the isolation and study of putative modifier genes in those animal and plant species where chromosomal imprinting has been described.

789

Images in this article

Selected References

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

  1. Aruffo A., Seed B. Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8573–8577. doi: 10.1073/pnas.84.23.8573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BROWN S. W., NUR U. HETEROCHROMATIC CHROMOSOMES IN THE COCCIDS. Science. 1964 Jul 10;145(3628):130–136. doi: 10.1126/science.145.3628.130. [DOI] [PubMed] [Google Scholar]
  3. Brown S. W. Heterochromatin. Science. 1966 Jan 28;151(3709):417–425. doi: 10.1126/science.151.3709.417. [DOI] [PubMed] [Google Scholar]
  4. Cattanach B. M., Kirk M. Differential activity of maternally and paternally derived chromosome regions in mice. Nature. 1985 Jun 6;315(6019):496–498. doi: 10.1038/315496a0. [DOI] [PubMed] [Google Scholar]
  5. Chandra H. S., Brown S. W. Chromosome imprinting and the mammalian X chromosome. Nature. 1975 Jan 17;253(5488):165–168. doi: 10.1038/253165a0. [DOI] [PubMed] [Google Scholar]
  6. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  7. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Crouse H V. The Controlling Element in Sex Chromosome Behavior in Sciara. Genetics. 1960 Oct;45(10):1429–1443. doi: 10.1093/genetics/45.10.1429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eissenberg J. C. Position effect variegation in Drosophila: towards a genetics of chromatin assembly. Bioessays. 1989 Jul;11(1):14–17. doi: 10.1002/bies.950110105. [DOI] [PubMed] [Google Scholar]
  11. Fahrner K., Hogan B. L., Flavell R. A. Transcription of H-2 and Qa genes in embryonic and adult mice. EMBO J. 1987 May;6(5):1265–1271. doi: 10.1002/j.1460-2075.1987.tb02363.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  13. Gaunt S. J. Homoeobox gene Hox-1.5 expression in mouse embryos: earliest detection by in situ hybridization is during gastrulation. Development. 1987 Sep;101(1):51–60. [PubMed] [Google Scholar]
  14. Gaunt S. J., Singh P. B. Homeogene expression patterns and chromosomal imprinting. Trends Genet. 1990 Jul;6(7):208–212. [PubMed] [Google Scholar]
  15. Gilbert W., Marchionni M., McKnight G. On the antiquity of introns. Cell. 1986 Jul 18;46(2):151–153. doi: 10.1016/0092-8674(86)90730-0. [DOI] [PubMed] [Google Scholar]
  16. Goldfarb D. S. Nuclear transport. Curr Opin Cell Biol. 1989 Jun;1(3):441–446. doi: 10.1016/0955-0674(89)90003-3. [DOI] [PubMed] [Google Scholar]
  17. Hall J. G. Genomic imprinting: review and relevance to human diseases. Am J Hum Genet. 1990 May;46(5):857–873. [PMC free article] [PubMed] [Google Scholar]
  18. Henikoff S. Position-effect variegation and chromosome structure of a heat shock puff in Drosophila. Chromosoma. 1981;83(3):381–393. doi: 10.1007/BF00327360. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Katsuki M., Sato M., Kimura M., Yokoyama M., Kobayashi K., Nomura T. Conversion of normal behavior to shiverer by myelin basic protein antisense cDNA in transgenic mice. Science. 1988 Jul 29;241(4865):593–595. doi: 10.1126/science.2456614. [DOI] [PubMed] [Google Scholar]
  21. Kornher J. S., Kauffman S. A. Variegated expression of the Sgs-4 locus in Drosophila melanogaster. Chromosoma. 1986;94(3):205–216. doi: 10.1007/BF00288495. [DOI] [PubMed] [Google Scholar]
  22. Laird C. D. Proposed genetic basis of Huntington's disease. Trends Genet. 1990 Aug;6(8):242–247. doi: 10.1016/0168-9525(90)90206-l. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Lyon M. F., Rastan S. Parental source of chromosome imprinting and its relevance for X chromosome inactivation. Differentiation. 1984;26(1):63–67. doi: 10.1111/j.1432-0436.1984.tb01375.x. [DOI] [PubMed] [Google Scholar]
  25. McGowan R., Campbell R., Peterson A., Sapienza C. Cellular mosaicism in the methylation and expression of hemizygous loci in the mouse. Genes Dev. 1989 Nov;3(11):1669–1676. doi: 10.1101/gad.3.11.1669. [DOI] [PubMed] [Google Scholar]
  26. Megee P. C., Morgan B. A., Mittman B. A., Smith M. M. Genetic analysis of histone H4: essential role of lysines subject to reversible acetylation. Science. 1990 Feb 16;247(4944):841–845. doi: 10.1126/science.2106160. [DOI] [PubMed] [Google Scholar]
  27. Nix C. E. Suppression of transcription of the ribosomal RNA cistrons of Drosophila melanogaster in a structurally rearranged chromosome. Biochem Genet. 1973 Sep;10(1):1–12. doi: 10.1007/BF00485743. [DOI] [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. 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]
  30. Reuter G., Werner W., Hoffmann H. J. Mutants affecting position-effect heterochromatinization in Drosophila melanogaster. Chromosoma. 1982;85(4):539–551. doi: 10.1007/BF00327349. [DOI] [PubMed] [Google Scholar]
  31. Reuter G., Wolff I. Isolation of dominant suppressor mutations for position-effect variegation in Drosophila melanogaster. Mol Gen Genet. 1981;182(3):516–519. doi: 10.1007/BF00293947. [DOI] [PubMed] [Google Scholar]
  32. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sapienza C. Parental imprinting of genes. Sci Am. 1990 Oct;263(4):52–60. doi: 10.1038/scientificamerican1090-52. [DOI] [PubMed] [Google Scholar]
  34. Surani M. A., Barton S. C., Norris M. L. Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature. 1984 Apr 5;308(5959):548–550. doi: 10.1038/308548a0. [DOI] [PubMed] [Google Scholar]
  35. Sweetser D. A., Hauft S. M., Hoppe P. C., Birkenmeier E. H., Gordon J. I. Transgenic mice containing intestinal fatty acid-binding protein-human growth hormone fusion genes exhibit correct regional and cell-specific expression of the reporter gene in their small intestine. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9611–9615. doi: 10.1073/pnas.85.24.9611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Takagi N., Sasaki M. Preferential inactivation of the paternally derived X chromosome in the extraembryonic membranes of the mouse. Nature. 1975 Aug 21;256(5519):640–642. doi: 10.1038/256640a0. [DOI] [PubMed] [Google Scholar]
  37. Tartof K. D., Bishop C., Jones M., Hobbs C. A., Locke J. Towards an understanding of position effect variegation. Dev Genet. 1989;10(3):162–176. doi: 10.1002/dvg.1020100306. [DOI] [PubMed] [Google Scholar]
  38. Tartof K. D., Hobbs C., Jones M. A structural basis for variegating position effects. Cell. 1984 Jul;37(3):869–878. doi: 10.1016/0092-8674(84)90422-7. [DOI] [PubMed] [Google Scholar]
  39. Zink B., Paro R. In vivo binding pattern of a trans-regulator of homoeotic genes in Drosophila melanogaster. Nature. 1989 Feb 2;337(6206):468–471. doi: 10.1038/337468a0. [DOI] [PubMed] [Google Scholar]