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. 2002 Dec;162(4):1763–1774. doi: 10.1093/genetics/162.4.1763

A role for the Drosophila SU(VAR)3-9 protein in chromatin organization at the histone gene cluster and in suppression of position-effect variegation.

Sarbjit S Ner 1, Michael J Harrington 1, Thomas A Grigliatti 1
PMCID: PMC1462387  PMID: 12524347

Abstract

Mutations in the gene for Su(var)3-9 are dominant suppressors of position-effect variegation (PEV). We show that SU(VAR)3-9 is a chromatin-associated protein and identify the large multicopy histone gene cluster (HIS-C) as one of its target loci. The organization of nucleosomes over the entire HIS-C region is altered in Su(var)3-9 mutants and there is a concomitant increase in expression of the histone genes. SU(VAR)3-9 is a histone H3 methyltransferase and, using chromatin immunoprecipitation, we show that SU(VAR)3-9 is present at the HIS-C locus and that the histone H3 at the HIS-C locus is methylated. We propose that SU(VAR)3-9 is involved in packaging HIS-C into a distinct chromatin domain that has some of the characteristics of beta-heterochromatin. We suggest that methylation of histone H3 is important for the chromatin structure at HIS-C. The chromosomal deficiency for the HIS-C is also a suppressor of PEV. In contrast to what might be expected, we show that hemizygosity for the HIS-C locus leads to a substantial increase in the histone transcripts.

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Selected References

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  1. Ahmad Kami, Henikoff Steven. The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. Mol Cell. 2002 Jun;9(6):1191–1200. doi: 10.1016/s1097-2765(02)00542-7. [DOI] [PubMed] [Google Scholar]
  2. Boivin A., Dura J. M. In vivo chromatin accessibility correlates with gene silencing in Drosophila. Genetics. 1998 Dec;150(4):1539–1549. doi: 10.1093/genetics/150.4.1539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chernyshev A. I., Bashkirov V. N., Leibovitch B. A., Khesin R. B. Increase in the number of histone genes in case of their deficiency in Drosophila melanogaster. Mol Gen Genet. 1980;178(3):663–668. doi: 10.1007/BF00337876. [DOI] [PubMed] [Google Scholar]
  4. Croston G. E., Lira L. M., Kadonaga J. T. A general method for purification of H1 histones that are active for repression of basal RNA polymerase II transcription. Protein Expr Purif. 1991 Apr-Jun;2(2-3):162–169. doi: 10.1016/1046-5928(91)90066-r. [DOI] [PubMed] [Google Scholar]
  5. Cryderman D. E., Morris E. J., Biessmann H., Elgin S. C., Wallrath L. L. Silencing at Drosophila telomeres: nuclear organization and chromatin structure play critical roles. EMBO J. 1999 Jul 1;18(13):3724–3735. doi: 10.1093/emboj/18.13.3724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dernburg A. F., Broman K. W., Fung J. C., Marshall W. F., Philips J., Agard D. A., Sedat J. W. Perturbation of nuclear architecture by long-distance chromosome interactions. Cell. 1996 May 31;85(5):745–759. doi: 10.1016/s0092-8674(00)81240-4. [DOI] [PubMed] [Google Scholar]
  7. Fung J. C., Marshall W. F., Dernburg A., Agard D. A., Sedat J. W. Homologous chromosome pairing in Drosophila melanogaster proceeds through multiple independent initiations. J Cell Biol. 1998 Apr 6;141(1):5–20. doi: 10.1083/jcb.141.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Jacobs S. A., Taverna S. D., Zhang Y., Briggs S. D., Li J., Eissenberg J. C., Allis C. D., Khorasanizadeh S. Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3. EMBO J. 2001 Sep 17;20(18):5232–5241. doi: 10.1093/emboj/20.18.5232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. James T. C., Eissenberg J. C., Craig C., Dietrich V., Hobson A., Elgin S. C. Distribution patterns of HP1, a heterochromatin-associated nonhistone chromosomal protein of Drosophila. Eur J Cell Biol. 1989 Oct;50(1):170–180. [PubMed] [Google Scholar]
  12. Lifton R. P., Goldberg M. L., Karp R. W., Hogness D. S. The organization of the histone genes in Drosophila melanogaster: functional and evolutionary implications. Cold Spring Harb Symp Quant Biol. 1978;42(Pt 2):1047–1051. doi: 10.1101/sqb.1978.042.01.105. [DOI] [PubMed] [Google Scholar]
  13. Lohe A. R., Hilliker A. J. Return of the H-word (heterochromatin). Curr Opin Genet Dev. 1995 Dec;5(6):746–755. doi: 10.1016/0959-437x(95)80007-r. [DOI] [PubMed] [Google Scholar]
  14. Matsuo Y., Yamazaki T. tRNA derived insertion element in histone gene repeating unit of Drosophila melanogaster. Nucleic Acids Res. 1989 Jan 11;17(1):225–238. doi: 10.1093/nar/17.1.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Minc E., Courvalin J. C., Buendia B. HP1gamma associates with euchromatin and heterochromatin in mammalian nuclei and chromosomes. Cytogenet Cell Genet. 2000;90(3-4):279–284. doi: 10.1159/000056789. [DOI] [PubMed] [Google Scholar]
  16. Moore G. D., Procunier J. D., Cross D. P., Grigliatti T. A. Histone gene deficiencies and position--effect variegation in Drosophila. Nature. 1979 Nov 15;282(5736):312–314. doi: 10.1038/282312a0. [DOI] [PubMed] [Google Scholar]
  17. Moore G. D., Sinclair D. A., Grigliatti T. A. Histone Gene Multiplicity and Position Effect Variegation in DROSOPHILA MELANOGASTER. Genetics. 1983 Oct;105(2):327–344. doi: 10.1093/genetics/105.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nakayama J., Rice J. C., Strahl B. D., Allis C. D., Grewal S. I. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science. 2001 Mar 15;292(5514):110–113. doi: 10.1126/science.1060118. [DOI] [PubMed] [Google Scholar]
  19. Ner S. S., Travers A. A. HMG-D, the Drosophila melanogaster homologue of HMG 1 protein, is associated with early embryonic chromatin in the absence of histone H1. EMBO J. 1994 Apr 15;13(8):1817–1822. doi: 10.1002/j.1460-2075.1994.tb06450.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Noma K, Allis C. D., Grewal S. I. Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science. 2001 Aug 10;293(5532):1150–1155. doi: 10.1126/science.1064150. [DOI] [PubMed] [Google Scholar]
  21. Norris D., Dunn B., Osley M. A. The effect of histone gene deletions on chromatin structure in Saccharomyces cerevisiae. Science. 1988 Nov 4;242(4879):759–761. doi: 10.1126/science.2847314. [DOI] [PubMed] [Google Scholar]
  22. Osley M. A. The regulation of histone synthesis in the cell cycle. Annu Rev Biochem. 1991;60:827–861. doi: 10.1146/annurev.bi.60.070191.004143. [DOI] [PubMed] [Google Scholar]
  23. Platero J. S., Hartnett T., Eissenberg J. C. Functional analysis of the chromo domain of HP1. EMBO J. 1995 Aug 15;14(16):3977–3986. doi: 10.1002/j.1460-2075.1995.tb00069.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rea S., Eisenhaber F., O'Carroll D., Strahl B. D., Sun Z. W., Schmid M., Opravil S., Mechtler K., Ponting C. P., Allis C. D. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature. 2000 Aug 10;406(6796):593–599. doi: 10.1038/35020506. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Saigo K., Millstein L., Thomas C. A., Jr The organization of Drosophila melanogaster histone genes. Cold Spring Harb Symp Quant Biol. 1981;45(Pt 2):815–827. doi: 10.1101/sqb.1981.045.01.100. [DOI] [PubMed] [Google Scholar]
  27. Samal B., Worcel A., Louis C., Schedl P. Chromatin structure of the histone genes of D. melanogaster. Cell. 1981 Feb;23(2):401–409. doi: 10.1016/0092-8674(81)90135-5. [DOI] [PubMed] [Google Scholar]
  28. Samson M. L., Wegnez M. Bipartite structure of the 5S ribosomal gene family in a Drosophila melanogaster strain, and its evolutionary implications. Genetics. 1988 Apr;118(4):685–691. doi: 10.1093/genetics/118.4.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sauvé D. M., Anderson H. J., Ray J. M., James W. M., Roberge M. Phosphorylation-induced rearrangement of the histone H3 NH2-terminal domain during mitotic chromosome condensation. J Cell Biol. 1999 Apr 19;145(2):225–235. doi: 10.1083/jcb.145.2.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schlossherr J., Eggert H., Paro R., Cremer S., Jack R. S. Gene inactivation in Drosophila mediated by the Polycomb gene product or by position-effect variegation does not involve major changes in the accessibility of the chromatin fibre. Mol Gen Genet. 1994 May 25;243(4):453–462. doi: 10.1007/BF00280476. [DOI] [PubMed] [Google Scholar]
  31. Schotta Gunnar, Ebert Anja, Krauss Veiko, Fischer Andreas, Hoffmann Jan, Rea Stephen, Jenuwein Thomas, Dorn Rainer, Reuter Gunter. Central role of Drosophila SU(VAR)3-9 in histone H3-K9 methylation and heterochromatic gene silencing. EMBO J. 2002 Mar 1;21(5):1121–1131. doi: 10.1093/emboj/21.5.1121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sinclair D. A., Suzuki D. T., Grigliatti T. A. Genetic and developmental analysis of a temperature-sensitive minute mutation of Drosophila melanogaster. Genetics. 1981 Mar-Apr;97(3-4):581–606. doi: 10.1093/genetics/97.3-4.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Steyerberg E. W., Kievit J., de Mol Van Otterloo J. C., van Bockel J. H., Eijkemans M. J., Habbema J. D. Perioperative mortality of elective abdominal aortic aneurysm surgery. A clinical prediction rule based on literature and individual patient data. Arch Intern Med. 1995 Oct 9;155(18):1998–2004. [PubMed] [Google Scholar]
  34. Strutt H., Cavalli G., Paro R. Co-localization of Polycomb protein and GAGA factor on regulatory elements responsible for the maintenance of homeotic gene expression. EMBO J. 1997 Jun 16;16(12):3621–3632. doi: 10.1093/emboj/16.12.3621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Wallrath L. L., Elgin S. C. Position effect variegation in Drosophila is associated with an altered chromatin structure. Genes Dev. 1995 May 15;9(10):1263–1277. doi: 10.1101/gad.9.10.1263. [DOI] [PubMed] [Google Scholar]
  37. Weiler K. S., Wakimoto B. T. Heterochromatin and gene expression in Drosophila. Annu Rev Genet. 1995;29:577–605. doi: 10.1146/annurev.ge.29.120195.003045. [DOI] [PubMed] [Google Scholar]
  38. Wu C., Wong Y. C., Elgin S. C. The chromatin structure of specific genes: II. Disruption of chromatin structure during gene activity. Cell. 1979 Apr;16(4):807–814. doi: 10.1016/0092-8674(79)90096-5. [DOI] [PubMed] [Google Scholar]
  39. Wyrick J. J., Holstege F. C., Jennings E. G., Causton H. C., Shore D., Grunstein M., Lander E. S., Young R. A. Chromosomal landscape of nucleosome-dependent gene expression and silencing in yeast. Nature. 1999 Nov 25;402(6760):418–421. doi: 10.1038/46567. [DOI] [PubMed] [Google Scholar]

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