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PMID: 18515193 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The histone methylase Set2p and the histone deacetylase Rpd3p repress meiotic recombination at the HIS4 meiotic recombination hotspot in Saccharomyces cerevisiae.

DNA repair ·Vol. 7 ·No. 8 ·2008-08-02 ·Pages 1298-308

Merker JD, Dominska M, Greenwell PW, Rinella E, Bouck DC, Shibata Y, Strahl BD, Mieczkowski P, Petes TD

Abstract

The rate of meiotic recombination in the yeast Saccharomyces cerevisiae varies widely in different regions of the genome with some genes having very high levels of recombination (hotspots). A variety of experiments done in yeast suggest that hotspots are a feature of chromatin structure rather than a feature of primary DNA sequence. We examined the effects of mutating a variety of enzymes that affect chromatin structure on the recombination activity of the well-characterized HIS4 hotspot including the Set2p and Dot1p histone methylases, the Hda1p and Rpd3p histone deacetylases, the Sin4p global transcription regulator, and a deletion of one of the two copies of the genes encoding histone H3-H4. Loss of Set2p or Rpd3p substantially elevated HIS4 hotspot activity, and loss of Hda1p had a smaller stimulatory effect; none of the other alterations had a significant effect. The increase of HIS4 hotspot activity in set2 and rpd3 strains is likely to be related to the recent finding that histone H3 methylation by Set2p directs deacetylation of histones by Rpd3p.

MeSH Terms
Alcohol Oxidoreductases/genetics Aminohydrolases/genetics Base Sequence Chromatin Immunoprecipitation DNA Primers Histone Deacetylases/physiology Histones/physiology Meiosis/physiology Methyltransferases/physiology Pyrophosphatases/genetics Recombination, Genetic/physiology Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins/genetics,physiology
Chemicals
DNA Primers Histones Saccharomyces cerevisiae Proteins Alcohol Oxidoreductases HIS4 protein, S cerevisiae Methyltransferases Set2 protein, S cerevisiae RPD3 protein, S cerevisiae Histone Deacetylases Aminohydrolases Pyrophosphatases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Merker Jason D
Department of Biology, University of North Carolina, Chapel Hill, NC 27599-3280, USA.
Dominska Margaret
Greenwell Patricia W
Rinella Erica
Bouck David C
Shibata Yoichiro
Strahl Brian D
Mieczkowski Piotr
Petes Thomas D
References (60)
60 references, click to expand
  1. Meiosis-specific double-strand DNA breaks at the HIS4 recombination hot spot in the yeast Saccharomyces cerevisiae: control in cis and trans.
    Mol Cell Biol. 1995 Mar;15(3):1679-88 PMID: 7862159
  2. Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae.
    Microbiol Mol Biol Rev. 1999 Jun;63(2):349-404 PMID: 10357855
  3. Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain.
    Curr Biol. 2002 Jun 25;12(12):1052-8 PMID: 12123582
  4. Meiosis-induced double-strand break sites determined by yeast chromatin structure.
    Science. 1994 Jan 28;263(5146):515-8 PMID: 8290959
  5. Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11383-90 PMID: 11027339
  6. Microarray deacetylation maps determine genome-wide functions for yeast histone deacetylases.
    Cell. 2002 May 17;109(4):437-46 PMID: 12086601
  7. Phosphorylation of RNA polymerase II CTD regulates H3 methylation in yeast.
    Genes Dev. 2003 Mar 1;17(5):654-63 PMID: 12629047
  8. Meiotic recombination hot spots and cold spots.
    Nat Rev Genet. 2001 May;2(5):360-9 PMID: 11331902
  9. Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription.
    Cell. 2005 Nov 18;123(4):581-92 PMID: 16286007
  10. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae.
    Yeast. 1994 Dec;10(13):1793-808 PMID: 7747518
  11. Double-strand breaks at an initiation site for meiotic gene conversion.
    Nature. 1989 Mar 2;338(6210):87-90 PMID: 2645528
  12. Genome-wide binding map of the histone deacetylase Rpd3 in yeast.
    Nat Genet. 2002 Jul;31(3):248-54 PMID: 12089521
  13. A promoter deletion reduces the rate of mitotic, but not meiotic, recombination at the HIS4 locus in yeast.
    Curr Genet. 1992 Feb;21(2):109-16 PMID: 1568254
  14. ATP-dependent chromatin-remodeling complexes.
    Mol Cell Biol. 2000 Mar;20(6):1899-910 PMID: 10688638
  15. Highly specific antibodies determine histone acetylation site usage in yeast heterochromatin and euchromatin.
    Mol Cell. 2001 Aug;8(2):473-9 PMID: 11545749
  16. Relationship between nuclease-hypersensitive sites and meiotic recombination hot spot activity at the HIS4 locus of Saccharomyces cerevisiae.
    Mol Cell Biol. 1996 May;16(5):2037-43 PMID: 8628269
  17. Palindromic sequences in heteroduplex DNA inhibit mismatch repair in yeast.
    Nature. 1989 Jul 27;340(6231):318-20 PMID: 2546083
  18. HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that regulate silencing and transcription.
    Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14503-8 PMID: 8962081
  19. Changes in chromatin structure at recombination initiation sites during yeast meiosis.
    EMBO J. 1994 Dec 1;13(23):5754-63 PMID: 7988571
  20. Structure and function of the core histone N-termini: more than meets the eye.
    Biochemistry. 1998 Dec 22;37(51):17637-41 PMID: 9922128
  21. Maximal stimulation of meiotic recombination by a yeast transcription factor requires the transcription activation domain and a DNA-binding domain.
    Genetics. 1999 May;152(1):101-15 PMID: 10224246
  22. Regulation of HIS4 expression by the Saccharomyces cerevisiae SIN4 transcriptional regulator.
    Genetics. 1995 May;140(1):103-14 PMID: 7635278
  23. Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: a potential mechanism for position-effect variegation.
    Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1820-5 PMID: 12574507
  24. RAP1 is required for BAS1/BAS2- and GCN4-dependent transcription of the yeast HIS4 gene.
    Mol Cell Biol. 1991 Jul;11(7):3642-51 PMID: 1904543
  25. Alteration of nucleosome structure as a mechanism of transcriptional regulation.
    Annu Rev Biochem. 1998;67:545-79 PMID: 9759497
  26. The RNA polymerase II kinase Ctk1 regulates positioning of a 5' histone methylation boundary along genes.
    Mol Cell Biol. 2007 Jan;27(2):721-31 PMID: 17088384
  27. The Tn3 beta-lactamase gene acts as a hotspot for meiotic recombination in yeast.
    Genetics. 1991 Jan;127(1):39-51 PMID: 1849855
  28. Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family.
    Cell. 1997 Feb 7;88(3):375-84 PMID: 9039264
  29. HDA2 and HDA3 are related proteins that interact with and are essential for the activity of the yeast histone deacetylase HDA1.
    Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4391-6 PMID: 11287668
  30. Transcription factors are required for the meiotic recombination hotspot at the HIS4 locus in Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6621-5 PMID: 8341678
  31. Set1 is required for meiotic S-phase onset, double-strand break formation and middle gene expression.
    EMBO J. 2004 May 5;23(9):1957-67 PMID: 15071505
  32. The transcriptional program of sporulation in budding yeast.
    Science. 1998 Oct 23;282(5389):699-705 PMID: 9784122
  33. Communication between homologous chromosomes: genetic alterations at a nuclease-hypersensitive site can alter mitotic chromatin structure at that site both in cis and in trans.
    Genes Cells. 1996 May;1(5):475-89 PMID: 9078379
  34. Analysis of wild-type and rad50 mutants of yeast suggests an intimate relationship between meiotic chromosome synapsis and recombination.
    Cell. 1990 May 4;61(3):419-36 PMID: 2185891
  35. Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation.
    Mol Cell. 2005 Dec 22;20(6):971-8 PMID: 16364921
  36. DNA-binding protein RAP1 stimulates meiotic recombination at the HIS4 locus in yeast.
    Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9755-9 PMID: 1946399
  37. GCN5-dependent histone H3 acetylation and RPD3-dependent histone H4 deacetylation have distinct, opposing effects on IME2 transcription, during meiosis and during vegetative growth, in budding yeast.
    Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6835-40 PMID: 10359799
  38. Multiple sites for double-strand breaks in whole meiotic chromosomes of Saccharomyces cerevisiae.
    EMBO J. 1992 Sep;11(9):3441-7 PMID: 1324174
  39. Chromatin opening and transactivator potentiation by RAP1 in Saccharomyces cerevisiae.
    Mol Cell Biol. 1999 Aug;19(8):5279-88 PMID: 10409719
  40. Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association.
    Genes Dev. 2002 Jun 15;16(12):1518-27 PMID: 12080090
  41. Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression.
    Mol Cell Biol. 2002 Mar;22(5):1298-306 PMID: 11839797
  42. Chromosomal landscape of nucleosome-dependent gene expression and silencing in yeast.
    Nature. 1999 Nov 25;402(6760):418-21 PMID: 10586882
  43. Targeted recruitment of the Sin3-Rpd3 histone deacetylase complex generates a highly localized domain of repressed chromatin in vivo.
    Mol Cell Biol. 1998 Sep;18(9):5121-7 PMID: 9710596
  44. The language of covalent histone modifications.
    Nature. 2000 Jan 6;403(6765):41-5 PMID: 10638745
  45. Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks during meiosis.
    Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11380-5 PMID: 15280549
  46. Meiotic recombination hotspots.
    Annu Rev Genet. 1995;29:423-44 PMID: 8825482
  47. Control of meiotic recombination and gene expression in yeast by a simple repetitive DNA sequence that excludes nucleosomes.
    Mol Cell Biol. 1999 Nov;19(11):7661-71 PMID: 10523654
  48. Roles of histone acetylation and chromatin remodeling factor in a meiotic recombination hotspot.
    EMBO J. 2004 Apr 21;23(8):1792-803 PMID: 14988732
  49. Meiotic recombination frequencies are affected by nutritional states in Saccharomycescerevisiae.
    Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14524-9 PMID: 11724920
  50. Biochemical Mutants in the Smut Fungus Ustilago Maydis.
    Genetics. 1949 Sep;34(5):607-26 PMID: 17247336
  51. Three new dominant drug resistance cassettes for gene disruption in Saccharomyces cerevisiae.
    Yeast. 1999 Oct;15(14):1541-53 PMID: 10514571
  52. Functional discovery via a compendium of expression profiles.
    Cell. 2000 Jul 7;102(1):109-26 PMID: 10929718
  53. Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex.
    Cell. 2005 Nov 18;123(4):593-605 PMID: 16286008
  54. Physical detection of heteroduplexes during meiotic recombination in the yeast Saccharomyces cerevisiae.
    Mol Cell Biol. 1993 Apr;13(4):2324-31 PMID: 8455614
  55. The double-strand-break repair model for recombination.
    Cell. 1983 May;33(1):25-35 PMID: 6380756
  56. Genomewide studies of histone deacetylase function in yeast.
    Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13708-13 PMID: 11095743
  57. RPD3 (REC3) mutations affect mitotic recombination in Saccharomyces cerevisiae.
    Curr Genet. 1999 Mar;35(2):68-76 PMID: 10079324
  58. Genome-wide map of nucleosome acetylation and methylation in yeast.
    Cell. 2005 Aug 26;122(4):517-27 PMID: 16122420
  59. The meiotic recombination hot spot created by the single-base substitution ade6-M26 results in remodeling of chromatin structure in fission yeast.
    Genes Dev. 1997 Apr 1;11(7):876-86 PMID: 9106659
  60. The Mre11 complex is required for repair of hairpin-capped double-strand breaks and prevention of chromosome rearrangements.
    Cell. 2002 Jan 25;108(2):183-93 PMID: 11832209
Article Info
Journal
DNA repair
Abbr.
DNA Repair (Amst)
ISSN
1568-7864
Published
2008-08-02
Epub
2008-00-02
Pages
1298-308
Language
English
Region
Netherlands
NLM ID
101139138
PMCID
PMC2518087
Subset
IM
Grants
NIGMS NIH HHS · R01 GM068088 · United States
NIGMS NIH HHS · GM 68088 · United States
NIGMS NIH HHS · R01 GM024110 · United States
NIGMS NIH HHS · R01 GM024110-31 · United States
NIGMS NIH HHS · GM 24110 · United States
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