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. 2002 Oct;162(2):591–602. doi: 10.1093/genetics/162.2.591

The 2.1-kb inverted repeat DNA sequences flank the mat2,3 silent region in two species of Schizosaccharomyces and are involved in epigenetic silencing in Schizosaccharomyces pombe.

Gurjeet Singh 1, Amar J S Klar 1
PMCID: PMC1462298  PMID: 12399374

Abstract

The mat2,3 region of the fission yeast Schizosaccharomyces pombe exhibits a phenomenon of transcriptional silencing. This region is flanked by two identical DNA sequence elements, 2.1 kb in length, present in inverted orientation: IRL on the left and IRR on the right of the silent region. The repeats do not encode any ORF. The inverted repeat DNA region is also present in a newly identified related species, which we named S. kambucha. Interestingly, the left and right repeats share perfect identity within a species, but show approximately 2% bases interspecies variation. Deletion of IRL results in variegated expression of markers inserted in the silent region, while deletion of the IRR causes their derepression. When deletions of these repeats were genetically combined with mutations in different trans-acting genes previously shown to cause a partial defect in silencing, only mutations in clr1 and clr3 showed additive defects in silencing with the deletion of IRL. The rate of mat1 switching is also affected by deletion of repeats. The IRL or IRR deletion did not cause significant derepression of the mat2 or mat3 loci. These results implicate repeats for maintaining full repression of the mat2,3 region, for efficient mat1 switching, and further support the notion that multiple pathways cooperate to silence the mat2,3 domain.

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Selected References

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

  1. Bartolomei M. S., Tilghman S. M. Genomic imprinting in mammals. Annu Rev Genet. 1997;31:493–525. doi: 10.1146/annurev.genet.31.1.493. [DOI] [PubMed] [Google Scholar]
  2. Beach D. H., Klar A. J. Rearrangements of the transposable mating-type cassettes of fission yeast. EMBO J. 1984 Mar;3(3):603–610. doi: 10.1002/j.1460-2075.1984.tb01855.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boeke J. D., Trueheart J., Natsoulis G., Fink G. R. 5-Fluoroorotic acid as a selective agent in yeast molecular genetics. Methods Enzymol. 1987;154:164–175. doi: 10.1016/0076-6879(87)54076-9. [DOI] [PubMed] [Google Scholar]
  4. Bonifer C. Developmental regulation of eukaryotic gene loci: which cis-regulatory information is required? Trends Genet. 2000 Jul;16(7):310–315. doi: 10.1016/s0168-9525(00)02029-1. [DOI] [PubMed] [Google Scholar]
  5. Bresch C., Müller G., Egel R. Genes involved in meiosis and sporulation of a yeast. Mol Gen Genet. 1968;102(4):301–306. doi: 10.1007/BF00433721. [DOI] [PubMed] [Google Scholar]
  6. Bähler J., Wu J. Q., Longtine M. S., Shah N. G., McKenzie A., 3rd, Steever A. B., Wach A., Philippsen P., Pringle J. R. Heterologous modules for efficient and versatile PCR-based gene targeting in Schizosaccharomyces pombe. Yeast. 1998 Jul;14(10):943–951. doi: 10.1002/(SICI)1097-0061(199807)14:10<943::AID-YEA292>3.0.CO;2-Y. [DOI] [PubMed] [Google Scholar]
  7. Cai H. N., Shen P. Effects of cis arrangement of chromatin insulators on enhancer-blocking activity. Science. 2001 Jan 19;291(5503):493–495. doi: 10.1126/science.291.5503.493. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Egel R. Mating-type switching and mitotic crossing-over at the mating-type locus in fission yeast. Cold Spring Harb Symp Quant Biol. 1981;45(Pt 2):1003–1007. doi: 10.1101/sqb.1981.045.01.116. [DOI] [PubMed] [Google Scholar]
  10. Ekwall K., Nielsen O., Ruusala T. Repression of a mating type cassette in the fission yeast by four DNA elements. Yeast. 1991 Oct;7(7):745–755. doi: 10.1002/yea.320070709. [DOI] [PubMed] [Google Scholar]
  11. Ekwall K., Ruusala T. Mutations in rik1, clr2, clr3 and clr4 genes asymmetrically derepress the silent mating-type loci in fission yeast. Genetics. 1994 Jan;136(1):53–64. doi: 10.1093/genetics/136.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Garrick D., Fiering S., Martin D. I., Whitelaw E. Repeat-induced gene silencing in mammals. Nat Genet. 1998 Jan;18(1):56–59. doi: 10.1038/ng0198-56. [DOI] [PubMed] [Google Scholar]
  13. Gottschling D. E., Aparicio O. M., Billington B. L., Zakian V. A. Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell. 1990 Nov 16;63(4):751–762. doi: 10.1016/0092-8674(90)90141-z. [DOI] [PubMed] [Google Scholar]
  14. Grewal S. I., Bonaduce M. J., Klar A. J. Histone deacetylase homologs regulate epigenetic inheritance of transcriptional silencing and chromosome segregation in fission yeast. Genetics. 1998 Oct;150(2):563–576. doi: 10.1093/genetics/150.2.563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Grewal S. I., Klar A. J. A recombinationally repressed region between mat2 and mat3 loci shares homology to centromeric repeats and regulates directionality of mating-type switching in fission yeast. Genetics. 1997 Aug;146(4):1221–1238. doi: 10.1093/genetics/146.4.1221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Grewal S. I., Klar A. J. Chromosomal inheritance of epigenetic states in fission yeast during mitosis and meiosis. Cell. 1996 Jul 12;86(1):95–101. doi: 10.1016/s0092-8674(00)80080-x. [DOI] [PubMed] [Google Scholar]
  17. Grewal S. I. Transcriptional silencing in fission yeast. J Cell Physiol. 2000 Sep;184(3):311–318. doi: 10.1002/1097-4652(200009)184:3<311::AID-JCP4>3.0.CO;2-D. [DOI] [PubMed] [Google Scholar]
  18. Heyer W. D., Sipiczki M., Kohli J. Replicating plasmids in Schizosaccharomyces pombe: improvement of symmetric segregation by a new genetic element. Mol Cell Biol. 1986 Jan;6(1):80–89. doi: 10.1128/mcb.6.1.80. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ivanova A. V., Bonaduce M. J., Ivanov S. V., Klar A. J. The chromo and SET domains of the Clr4 protein are essential for silencing in fission yeast. Nat Genet. 1998 Jun;19(2):192–195. doi: 10.1038/566. [DOI] [PubMed] [Google Scholar]
  20. Kelly M., Burke J., Smith M., Klar A., Beach D. Four mating-type genes control sexual differentiation in the fission yeast. EMBO J. 1988 May;7(5):1537–1547. doi: 10.1002/j.1460-2075.1988.tb02973.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Klar A. J., Bonaduce M. J. swi6, a gene required for mating-type switching, prohibits meiotic recombination in the mat2-mat3 "cold spot" of fission yeast. Genetics. 1991 Dec;129(4):1033–1042. doi: 10.1093/genetics/129.4.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lorentz A., Heim L., Schmidt H. The switching gene swi6 affects recombination and gene expression in the mating-type region of Schizosaccharomyces pombe. Mol Gen Genet. 1992 Jun;233(3):436–442. doi: 10.1007/BF00265441. [DOI] [PubMed] [Google Scholar]
  23. Lorentz A., Ostermann K., Fleck O., Schmidt H. Switching gene swi6, involved in repression of silent mating-type loci in fission yeast, encodes a homologue of chromatin-associated proteins from Drosophila and mammals. Gene. 1994 May 27;143(1):139–143. doi: 10.1016/0378-1119(94)90619-x. [DOI] [PubMed] [Google Scholar]
  24. Luff B., Pawlowski L., Bender J. An inverted repeat triggers cytosine methylation of identical sequences in Arabidopsis. Mol Cell. 1999 Apr;3(4):505–511. doi: 10.1016/s1097-2765(00)80478-5. [DOI] [PubMed] [Google Scholar]
  25. Luria S. E., Delbrück M. Mutations of Bacteria from Virus Sensitivity to Virus Resistance. Genetics. 1943 Nov;28(6):491–511. doi: 10.1093/genetics/28.6.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Matzke A. J., Neuhuber F., Park Y. D., Ambros P. F., Matzke M. A. Homology-dependent gene silencing in transgenic plants: epistatic silencing loci contain multiple copies of methylated transgenes. Mol Gen Genet. 1994 Aug 2;244(3):219–229. doi: 10.1007/BF00285449. [DOI] [PubMed] [Google Scholar]
  27. Max E. E., Seidman J. G., Leder P. Sequences of five potential recombination sites encoded close to an immunoglobulin kappa constant region gene. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3450–3454. doi: 10.1073/pnas.76.7.3450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mette M. F., van der Winden J., Matzke M. A., Matzke A. J. Production of aberrant promoter transcripts contributes to methylation and silencing of unlinked homologous promoters in trans. EMBO J. 1999 Jan 4;18(1):241–248. doi: 10.1093/emboj/18.1.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mittelsten Scheid O., Afsar K., Paszkowski J. Release of epigenetic gene silencing by trans-acting mutations in Arabidopsis. Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):632–637. doi: 10.1073/pnas.95.2.632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Moreno S., Klar A., Nurse P. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 1991;194:795–823. doi: 10.1016/0076-6879(91)94059-l. [DOI] [PubMed] [Google Scholar]
  31. Muravyova E., Golovnin A., Gracheva E., Parshikov A., Belenkaya T., Pirrotta V., Georgiev P. Loss of insulator activity by paired Su(Hw) chromatin insulators. Science. 2001 Jan 19;291(5503):495–498. doi: 10.1126/science.291.5503.495. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. Nimmo E. R., Cranston G., Allshire R. C. Telomere-associated chromosome breakage in fission yeast results in variegated expression of adjacent genes. EMBO J. 1994 Aug 15;13(16):3801–3811. doi: 10.1002/j.1460-2075.1994.tb06691.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Olsson T. G., Ekwall K., Allshire R. C., Sunnerhagen P., Partridge J. F., Richardson W. A. Genetic characterisation of hda1+, a putative fission yeast histone deacetylase gene. Nucleic Acids Res. 1998 Jul 1;26(13):3247–3254. doi: 10.1093/nar/26.13.3247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Selker E. U. Gene silencing: repeats that count. Cell. 1999 Apr 16;97(2):157–160. doi: 10.1016/s0092-8674(00)80725-4. [DOI] [PubMed] [Google Scholar]
  38. Singh P. B. Molecular mechanisms of cellular determination: their relation to chromatin structure and parental imprinting. J Cell Sci. 1994 Oct;107(Pt 10):2653–2668. doi: 10.1242/jcs.107.10.2653. [DOI] [PubMed] [Google Scholar]
  39. Stam M., Viterbo A., Mol J. N., Kooter J. M. Position-dependent methylation and transcriptional silencing of transgenes in inverted T-DNA repeats: implications for posttranscriptional silencing of homologous host genes in plants. Mol Cell Biol. 1998 Nov;18(11):6165–6177. doi: 10.1128/mcb.18.11.6165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Stam M., de Bruin R., van Blokland R., van der Hoorn R. A., Mol J. N., Kooter J. M. Distinct features of post-transcriptional gene silencing by antisense transgenes in single copy and inverted T-DNA repeat loci. Plant J. 2000 Jan;21(1):27–42. doi: 10.1046/j.1365-313x.2000.00650.x. [DOI] [PubMed] [Google Scholar]
  41. Steiner N. C., Clarke L. A novel epigenetic effect can alter centromere function in fission yeast. Cell. 1994 Dec 2;79(5):865–874. doi: 10.1016/0092-8674(94)90075-2. [DOI] [PubMed] [Google Scholar]
  42. Styrkársdóttir U., Egel R., Nielsen O. The smt-0 mutation which abolishes mating-type switching in fission yeast is a deletion. Curr Genet. 1993 Feb;23(2):184–186. doi: 10.1007/BF00352020. [DOI] [PubMed] [Google Scholar]
  43. Takahashi K., Murakami S., Chikashige Y., Funabiki H., Niwa O., Yanagida M. A low copy number central sequence with strict symmetry and unusual chromatin structure in fission yeast centromere. Mol Biol Cell. 1992 Jul;3(7):819–835. doi: 10.1091/mbc.3.7.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Thon G., Bjerling K. P., Nielsen I. S. Localization and properties of a silencing element near the mat3-M mating-type cassette of Schizosaccharomyces pombe. Genetics. 1999 Mar;151(3):945–963. doi: 10.1093/genetics/151.3.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Thon G., Cohen A., Klar A. J. Three additional linkage groups that repress transcription and meiotic recombination in the mating-type region of Schizosaccharomyces pombe. Genetics. 1994 Sep;138(1):29–38. doi: 10.1093/genetics/138.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Thon G., Klar A. J. Directionality of fission yeast mating-type interconversion is controlled by the location of the donor loci. Genetics. 1993 Aug;134(4):1045–1054. doi: 10.1093/genetics/134.4.1045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Thon G., Klar A. J. The clr1 locus regulates the expression of the cryptic mating-type loci of fission yeast. Genetics. 1992 Jun;131(2):287–296. doi: 10.1093/genetics/131.2.287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Thon Geneviève, Bjerling Pernilla, Bünner Camilla Marie, Verhein-Hansen Janne. Expression-state boundaries in the mating-type region of fission yeast. Genetics. 2002 Jun;161(2):611–622. doi: 10.1093/genetics/161.2.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Wassenegger M., Heimes S., Riedel L., Sänger H. L. RNA-directed de novo methylation of genomic sequences in plants. Cell. 1994 Feb 11;76(3):567–576. doi: 10.1016/0092-8674(94)90119-8. [DOI] [PubMed] [Google Scholar]
  50. West Adam G., Gaszner Miklos, Felsenfeld Gary. Insulators: many functions, many mechanisms. Genes Dev. 2002 Feb 1;16(3):271–288. doi: 10.1101/gad.954702. [DOI] [PubMed] [Google Scholar]
  51. Widom J. Chromatin structure: linking structure to function with histone H1. Curr Biol. 1998 Nov 5;8(22):R788–R791. doi: 10.1016/s0960-9822(07)00500-3. [DOI] [PubMed] [Google Scholar]
  52. Ye F., Signer E. R. RIGS (repeat-induced gene silencing) in Arabidopsis is transcriptional and alters chromatin configuration. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10881–10886. doi: 10.1073/pnas.93.20.10881. [DOI] [PMC free article] [PubMed] [Google Scholar]

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