Histone Methyltransferases MES-4 and MET-1 Promote Meiotic Checkpoint Activation in

English version České info

Chromosomes that fail to synapse during meiosis become enriched for chromatin marks associated with heterochromatin assembly. This response, called meiotic silencing of unsynapsed or unpaired chromatin (MSUC), is conserved from fungi to mammals. In Caenorhabditis elegans, unsynapsed chromosomes also activate a meiotic checkpoint that monitors synapsis. The synapsis checkpoint signal is dependent on cis-acting loci called Pairing Centers (PCs). How PCs signal to activate the synapsis checkpoint is currently unknown. We show that a chromosomal duplication with PC activity is sufficient to activate the synapsis checkpoint and that it undergoes heterochromatin assembly less readily than a duplication of a non-PC region, suggesting that the chromatin state of these loci is important for checkpoint function. Consistent with this hypothesis, MES-4 and MET-1, chromatin-modifying enzymes associated with transcriptional activity, are required for the synapsis checkpoint. In addition, a duplication with PC activity undergoes heterochromatin assembly when mes-4 activity is reduced. MES-4 function is required specifically for the X chromosome, while MES-4 and MET-1 act redundantly to monitor autosomal synapsis. We propose that MES-4 and MET-1 antagonize heterochromatin assembly at PCs of unsynapsed chromosomes by promoting a transcriptionally permissive chromatin environment that is required for meiotic checkpoint function. Moreover, we suggest that different genetic requirements to monitor the behavior of sex chromosomes and autosomes allow for the lone unsynapsed X present in male germlines to be shielded from inappropriate checkpoint activation.

Vyšlo v časopise: Histone Methyltransferases MES-4 and MET-1 Promote Meiotic Checkpoint Activation in. PLoS Genet 8(11): e32767. doi:10.1371/journal.pgen.1003089
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003089

Souhrn

Zdroje

1. BhallaN, DernburgAF (2008) Prelude to a division. Annu Rev Cell Dev Biol 24: 397–424.

2. HassoldT, HuntP (2001) To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2: 280–291.

3. MacQueenAJ, HochwagenA (2011) Checkpoint mechanisms: the puppet masters of meiotic prophase. Trends in cell biology 21: 393–400.

4. BhallaN, DernburgAF (2005) A conserved checkpoint monitors meiotic chromosome synapsis in Caenorhabditis elegans. Science 310: 1683–1686.

5. MacQueenAJ, PhillipsCM, BhallaN, WeiserP, VilleneuveAM, et al. (2005) Chromosome Sites Play Dual Roles to Establish Homologous Synapsis during Meiosis in C. elegans. Cell 123: 1037–1050.

6. PhillipsCM, DernburgAF (2006) A family of zinc-finger proteins is required for chromosome-specific pairing and synapsis during meiosis in C. elegans. Dev Cell 11: 817–829.

7. PhillipsCM, WongC, BhallaN, CarltonPM, WeiserP, et al. (2005) HIM-8 Binds to the X Chromosome Pairing Center and Mediates Chromosome-Specific Meiotic Synapsis. Cell 123: 1051–1063.

8. BeanCJ, SchanerCE, KellyWG (2004) Meiotic pairing and imprinted X chromatin assembly in Caenorhabditis elegans. Nat Genet 36: 100–105.

9. ShiuPK, MetzenbergRL (2002) Meiotic silencing by unpaired DNA: properties, regulation and suppression. Genetics 161: 1483–1495.

10. TurnerJM, MahadevaiahSK, Fernandez-CapetilloO, NussenzweigA, XuX, et al. (2005) Silencing of unsynapsed meiotic chromosomes in the mouse. Nat Genet 37: 41–47.

11. TurnerJM (2007) Meiotic sex chromosome inactivation. Development 134: 1823–1831.

12. MahadevaiahSK, Bourc'hisD, de RooijDG, BestorTH, TurnerJM, et al. (2008) Extensive meiotic asynapsis in mice antagonises meiotic silencing of unsynapsed chromatin and consequently disrupts meiotic sex chromosome inactivation. J Cell Biol 182: 263–276.

13. RoyoH, PolikiewiczG, MahadevaiahSK, ProsserH, MitchellM, et al. (2010) Evidence that meiotic sex chromosome inactivation is essential for male fertility. Current biology: CB 20: 2117–2123.

14. BurgoynePS, MahadevaiahSK, TurnerJM (2009) The consequences of asynapsis for mammalian meiosis. Nat Rev Genet 10: 207–216.

15. ChecchiPM, EngebrechtJ (2011) Caenorhabditis elegans histone methyltransferase MET-2 shields the male X chromosome from checkpoint machinery and mediates meiotic sex chromosome inactivation. PLoS Genet 7: e1002267 doi:10.1371/journal.pgen.1002267.

16. Jaramillo-LambertA, EngebrechtJ (2010) A single unpaired and transcriptionally silenced X chromosome locally precludes checkpoint signaling in the Caenorhabditis elegans germ line. Genetics 184: 613–628.

17. BesslerJB, AndersenEC, VilleneuveAM (2010) Differential localization and independent acquisition of the H3K9me2 and H3K9me3 chromatin modifications in the Caenorhabditis elegans adult germ line. PLoS Genet 6: e1000830 doi:10.1371/journal.pgen.1000830.

18. SheX, XuX, FedotovA, KellyWG, MaineEM (2009) Regulation of heterochromatin assembly on unpaired chromosomes during Caenorhabditis elegans meiosis by components of a small RNA-mediated pathway. PLoS Genet 5: e1000624 doi:10.1371/journal.pgen.1000624.

19. MaineEM, HauthJ, RatliffT, VoughtVE, SheX, et al. (2005) EGO-1, a putative RNA-dependent RNA polymerase, is required for heterochromatin assembly on unpaired dna during C. elegans meiosis. Current biology: CB 15: 1972–1978.

20. RechtsteinerA, ErcanS, TakasakiT, PhippenTM, EgelhoferTA, et al. (2010) The histone H3K36 methyltransferase MES-4 acts epigenetically to transmit the memory of germline gene expression to progeny. PLoS Genet 6: e1001091 doi:10.1371/journal.pgen.1001091.

21. CapowskiEE, MartinP, GarvinC, StromeS (1991) Identification of grandchildless loci whose products are required for normal germ-line development in the nematode Caenorhabditis elegans. Genetics 129: 1061–1072.

22. FongY, BenderL, WangW, StromeS (2002) Regulation of the different chromatin states of autosomes and X chromosomes in the germ line of C. elegans. Science 296: 2235–2238.

23. CarrozzaMJ, LiB, FlorensL, SuganumaT, SwansonSK, et al. (2005) Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell 123: 581–592.

24. JoshiAA, StruhlK (2005) Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation. Molecular cell 20: 971–978.

25. KeoghMC, KurdistaniSK, MorrisSA, AhnSH, PodolnyV, et al. (2005) Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell 123: 593–605.

26. AndersenEC, HorvitzHR (2007) Two C. elegans histone methyltransferases repress lin-3 EGF transcription to inhibit vulval development. Development 134: 2991–2999.

27. VilleneuveAM (1994) A cis-acting locus that promotes crossing over between X chromosomes in Caenorhabditis elegans. Genetics 136: 887–902.

28. MacQueenAJ, VilleneuveAM (2001) Nuclear reorganization and homologous chromosome pairing during meiotic prophase require C. elegans chk-2. Genes Dev 15: 1674–1687.

29. HermanRK, KariCK (1989) Recombination between small X chromosome duplications and the X chromosome in Caenorhabditis elegans. Genetics 121: 723–737.

30. HermanRK, AlbertsonDG, BrennerS (1976) Chromosome rearrangements in Caenorhabditis elegans. Genetics 83: 91–105.

31. HofmannER, MilsteinS, BoultonSJ, YeM, HofmannJJ, et al. (2002) Caenorhabditis elegans HUS-1 is a DNA damage checkpoint protein required for genome stability and EGL-1-mediated apoptosis. Curr Biol 12: 1908–1918.

32. GarvinC, HoldemanR, StromeS (1998) The phenotype of mes-2, mes-3, mes-4 and mes-6, maternal-effect genes required for survival of the germline in Caenorhabditis elegans, is sensitive to chromosome dosage. Genetics 148: 167–185.

33. BenderLB, SuhJ, CarrollCR, FongY, FingermanIM, et al. (2006) MES-4: an autosome-associated histone methyltransferase that participates in silencing the X chromosomes in the C. elegans germ line. Development 133: 3907–3917.

34. GaydosL, RechtsteinerA, EgelhoferTA, CarrollC, StromeS (2012) Antagonism between MES-4 and the C. elegans Polycomb Repressive Complex 2 Promotes Germ Cell-Appropriate Gene Expression. Cell Rep in press.

35. HoldemanR, NehrtS, StromeS (1998) MES-2, a maternal protein essential for viability of the germline in Caenorhabditis elegans, is homologous to a Drosophila Polycomb group protein. Development 125: 2457–2467.

36. BenderLB, CaoR, ZhangY, StromeS (2004) The MES-2/MES-3/MES-6 complex and regulation of histone H3 methylation in C. elegans. Current biology: CB 14: 1639–1643.

37. KetelCS, AndersenEF, VargasML, SuhJ, StromeS, et al. (2005) Subunit contributions to histone methyltransferase activities of fly and worm polycomb group complexes. Molecular and cellular biology 25: 6857–6868.

38. HarperNC, RilloR, Jover-GilS, AssafZJ, BhallaN, et al. (2011) Pairing centers recruit a Polo-like kinase to orchestrate meiotic chromosome dynamics in C. elegans. Developmental cell 21: 934–947.

39. PenknerAM, FridkinA, GloggnitzerJ, BaudrimontA, MachacekT, et al. (2009) Meiotic chromosome homology search involves modifications of the nuclear envelope protein Matefin/SUN-1. Cell 139: 920–933.

40. XuJ, SunX, JingY, WangM, LiuK, et al. (2012) MRG-1 is required for genomic integrity in Caenorhabditis elegans germ cells. Cell research

41. ColaiacovoMP, MacQueenAJ, Martinez-PerezE, McDonaldK, AdamoA, et al. (2003) Synaptonemal complex assembly in C. elegans is dispensable for loading strand-exchange proteins but critical for proper completion of recombination. Developmental cell 5: 463–474.

42. DudleyNR, LabbeJC, GoldsteinB (2002) Using RNA interference to identify genes required for RNA interference. Proc Natl Acad Sci U S A 99: 4191–4196.

43. XuL, StromeS (2001) Depletion of a novel SET-domain protein enhances the sterility of mes-3 and mes-4 mutants of Caenorhabditis elegans. Genetics 159: 1019–1029.

44. WhetstineJR, NottkeA, LanF, HuarteM, SmolikovS, et al. (2006) Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell 125: 467–481.

45. KellyWG, SchanerCE, DernburgAF, LeeMH, KimSK, et al. (2002) X-chromosome silencing in the germline of C. elegans. Development 129: 479–492.

46. SchanerCE, KellyWG (2006) Germline chromatin. WormBook: the online review of C elegans biology 1–14.

47. TabuchiTM, DeplanckeB, OsatoN, ZhuLJ, BarrasaMI, et al. (2011) Chromosome-biased binding and gene regulation by the Caenorhabditis elegans DRM complex. PLoS Genet 7: e1002074 doi:10.1371/journal.pgen.1002074.

48. WangX, ZhaoY, WongK, EhlersP, KoharaY, et al. (2009) Identification of genes expressed in the hermaphrodite germ line of C. elegans using SAGE. BMC Genomics 10: 213.

49. PhillipsCM, MengX, ZhangL, ChretienJH, UrnovFD, et al. (2009) Identification of chromosome sequence motifs that mediate meiotic pairing and synapsis in C. elegans. Nat Cell Biol 11: 934–942.

50. LabellaS, WoglarA, JantschV, ZetkaM (2011) Polo kinases establish links between meiotic chromosomes and cytoskeletal forces essential for homolog pairing. Developmental cell 21: 948–958.

51. PenknerA, TangL, NovatchkovaM, LadurnerM, FridkinA, et al. (2007) The nuclear envelope protein Matefin/SUN-1 is required for homologous pairing in C. elegans meiosis. Dev Cell 12: 873–885.

52. SatoA, IsaacB, PhillipsCM, RilloR, CarltonPM, et al. (2009) Cytoskeletal forces span the nuclear envelope to coordinate meiotic chromosome pairing and synapsis. Cell 139: 907–919.

53. NelmsBL, Hanna-RoseW (2006) C. elegans HIM-8 functions outside of meiosis to antagonize EGL-13 Sox protein function. Developmental biology 293: 392–402.

54. SunH, NelmsBL, SleimanSF, ChamberlinHM, Hanna-RoseW (2007) Modulation of Caenorhabditis elegans transcription factor activity by HIM-8 and the related Zinc-Finger ZIM proteins. Genetics 177: 1221–1226.

55. DernburgAF (2001) Here, there, and everywhere: kinetochore function on holocentric chromosomes. J Cell Biol 153: F33–38.

56. OhkuniK, KitagawaK (2011) Endogenous transcription at the centromere facilitates centromere activity in budding yeast. Current biology: CB 21: 1695–1703.

57. DuY, ToppCN, DaweRK (2010) DNA binding of centromere protein C (CENPC) is stabilized by single-stranded RNA. PLoS Genet 6: e1000835 doi:10.1371/journal.pgen.1000835.

58. FukagawaT, NogamiM, YoshikawaM, IkenoM, OkazakiT, et al. (2004) Dicer is essential for formation of the heterochromatin structure in vertebrate cells. Nature cell biology 6: 784–791.

59. VolpeTA, KidnerC, HallIM, TengG, GrewalSI, et al. (2002) Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297: 1833–1837.

60. FolcoHD, PidouxAL, UranoT, AllshireRC (2008) Heterochromatin and RNAi are required to establish CENP-A chromatin at centromeres. Science 319: 94–97.

61. WuY, KikuchiS, YanH, ZhangW, RosenbaumH, et al. (2011) Euchromatic subdomains in rice centromeres are associated with genes and transcription. The Plant cell 23: 4054–4064.

62. SullivanBA, KarpenGH (2004) Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin. Nature structural & molecular biology 11: 1076–1083.

63. BergmannJH, RodriguezMG, MartinsNM, KimuraH, KellyDA, et al. (2011) Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore. The EMBO journal 30: 328–340.

64. ChanFL, MarshallOJ, SafferyR, KimBW, EarleE, et al. (2012) Active transcription and essential role of RNA polymerase II at the centromere during mitosis. Proceedings of the National Academy of Sciences of the United States of America 109: 1979–1984.

65. ChoiES, StralforsA, CastilloAG, Durand-DubiefM, EkwallK, et al. (2011) Identification of noncoding transcripts from within CENP-A chromatin at fission yeast centromeres. The Journal of biological chemistry 286: 23600–23607.

66. SafferyR, SumerH, HassanS, WongLH, CraigJM, et al. (2003) Transcription within a functional human centromere. Molecular cell 12: 509–516.

67. ChuehAC, NorthropEL, Brettingham-MooreKH, ChooKH, WongLH (2009) LINE retrotransposon RNA is an essential structural and functional epigenetic component of a core neocentromeric chromatin. PLoS Genet 5: e1000354 doi:10.1371/journal.pgen.1000354.

68. LiR, MurrayAW (1991) Feedback control of mitosis in budding yeast. Cell 66: 519–531.

69. TakasakiT, LiuZ, HabaraY, NishiwakiK, NakayamaJ, et al. (2007) MRG-1, an autosome-associated protein, silences X-linked genes and protects germline immortality in Caenorhabditis elegans. Development 134: 757–767.

70. DombeckiCR, ChiangAC, KangHJ, BilgirC, StefanskiNA, et al. (2011) The chromodomain protein MRG-1 facilitates SC-independent homologous pairing during meiosis in Caenorhabditis elegans. Developmental cell 21: 1092–1103.

71. KouzaridesT (2002) Histone methylation in transcriptional control. Current opinion in genetics & development 12: 198–209.

72. RoseAM, BaillieDL, CurranJ (1984) Meiotic pairing behavior of two free duplications of linkage group I in Caenorhabditis elegans. Molecular & general genetics: MGG 195: 52–56.

73. RathertP, DhayalanA, MaH, JeltschA (2008) Specificity of protein lysine methyltransferases and methods for detection of lysine methylation of non-histone proteins. Mol Biosyst 4: 1186–1190.

74. Consortium CeS (1998) Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282: 2012–2018.

75. CouteauF, NabeshimaK, VilleneuveA, ZetkaM (2004) A component of C. elegans meiotic chromosome axes at the interface of homolog alignment, synapsis, nuclear reorganization, and recombination. Curr Biol 14: 585–592.

76. ReddyKC, VilleneuveAM (2004) C. elegans HIM-17 links chromatin modification and competence for initiation of meiotic recombination. Cell 118: 439–452.

77. Martinez-PerezE, VilleneuveAM (2005) HTP-1-dependent constraints coordinate homolog pairing and synapsis and promote chiasma formation during C. elegans meiosis. Genes Dev 19: 2727–2743.

78. MeyerBJ (2000) Sex in the wormcounting and compensating X-chromosome dose. Trends in genetics: TIG 16: 247–253.

79. GumiennyTL, LambieE, HartwiegE, HorvitzHR, HengartnerMO (1999) Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline. Development 126: 1011–1022.

80. Jaramillo-LambertA, HarigayaY, VittJ, VilleneuveA, EngebrechtJ (2010) Meiotic errors activate checkpoints that improve gamete quality without triggering apoptosis in male germ cells. Current biology: CB 20: 2078–2089.

81. ReddienPW, BermangeAL, MurfittKJ, JenningsJR, Sanchez AlvaradoA (2005) Identification of genes needed for regeneration, stem cell function, and tissue homeostasis by systematic gene perturbation in planaria. Developmental cell 8: 635–649.

82. EgelhoferTA, MinodaA, KlugmanS, LeeK, Kolasinska-ZwierzP, et al. (2011) An assessment of histone-modification antibody quality. Nature structural & molecular biology 18: 91–93.