DOT-1.1-dependent H3K79 methylation promotes normal meiotic progression and meiotic checkpoint function in C. elegans


Autoři: Laura I. Lascarez-Lagunas aff001;  Esther Herruzo aff002;  Alla Grishok aff003;  Pedro A. San-Segundo aff002;  Mónica P. Colaiácovo aff001
Působiště autorů: Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, United States of America aff001;  Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas and University of Salamanca, Salamanca, Spain aff002;  Department of Biochemistry, Boston University School of Medicine, Boston, MA, United States of America aff003;  Genome Science Institute, Boston University School of Medicine, Boston, MA, United States of America aff004
Vyšlo v časopise: DOT-1.1-dependent H3K79 methylation promotes normal meiotic progression and meiotic checkpoint function in C. elegans. PLoS Genet 16(10): e32767. doi:10.1371/journal.pgen.1009171
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009171

Souhrn

Epigenetic modifiers are emerging as important regulators of the genome. However, how they regulate specific processes during meiosis is not well understood. Methylation of H3K79 by the histone methyltransferase Dot1 has been shown to be involved in the maintenance of genomic stability in various organisms. In S. cerevisiae, Dot1 modulates the meiotic checkpoint response triggered by synapsis and/or recombination defects by promoting Hop1-dependent Mek1 activation and Hop1 distribution along unsynapsed meiotic chromosomes, at least in part, by regulating Pch2 localization. However, how this protein regulates meiosis in metazoans is unknown. Here, we describe the effects of H3K79me depletion via analysis of dot-1.1 or zfp-1 mutants during meiosis in Caenorhabditis elegans. We observed decreased fertility and increased embryonic lethality in dot-1.1 mutants suggesting meiotic dysfunction. We show that DOT-1.1 plays a role in the regulation of pairing, synapsis and recombination in the worm. Furthermore, we demonstrate that DOT-1.1 is an important regulator of mechanisms surveilling chromosome synapsis during meiosis. In sum, our results reveal that regulation of H3K79me plays an important role in coordinating events during meiosis in C. elegans.

Klíčová slova:

Apoptosis – Caenorhabditis elegans – Gonads – Chromatin – Meiosis – Oocytes – Synapsis – Yeast


Zdroje

1. Baudat F, Imai Y, de Massy B. Meiotic recombination in mammals: localization and regulation. Nat. Rev. Genet. 2013;14:794–806. doi: 10.1038/nrg3573 24136506

2. Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat. Rev. Genet. 2001;2:280–291. doi: 10.1038/35066065 11283700

3. Van Holde KE, Allen JR, Tatchell K, Weischet WO, Lohr D. DNA-histone interactions in nucleosomes. Biophys J. 1980;32:271–282. doi: 10.1016/S0006-3495(80)84956-3 6788105

4. Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature. 1997;389:251–260. doi: 10.1038/38444 9305837

5. Kornberg RD, Lorch Y. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell. 1999;98:285–294. doi: 10.1016/s0092-8674(00)81958-3 10458604

6. Zhang K, Dent SYR. Histone modifying enzymes and cancer: going beyond histones. J Cell Biochem. 2005;96:1137–1148. doi: 10.1002/jcb.20615 16173079

7. Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403:41–45. doi: 10.1038/47412 10638745

8. Martin C, Zhang Y. The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol. 2005;6:838–849. doi: 10.1038/nrm1761 16261189

9. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128:693–705. doi: 10.1016/j.cell.2007.02.005 17320507

10. van Leeuwen F, Gafken PR, Gottschling DE. Dot1p modulates silencing in yeast by methylation of the nucleosome core. Cell. 2002;109:745–756. doi: 10.1016/s0092-8674(02)00759-6 12086673

11. Feng Q, Wang H, Ng HH, Erdjument-Bromage H, Tempst P, Struhl K, et al. Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain. Curr Biol. 2002;12:1052–1058. doi: 10.1016/s0960-9822(02)00901-6 12123582

12. Ng HH, Xu R-M, Zhang Y, Struhl K. Ubiquitination of histone H2B by Rad6 is required for efficient Dot1-mediated methylation of histone H3 lysine 79. J Biol Chem. 2002;277:34655–34657. doi: 10.1074/jbc.C200433200 12167634

13. Wood A, Schneider J, Shilatifard A. Cross-talking histones: implications for the regulation of gene expression and DNA repair. Biochem Cell Biol. 2005;83:460–467. doi: 10.1139/o05-116 16094449

14. Mohan M, Herz H-M, Takahashi Y-H, Lin C, Lai KC, Zhang Y, et al. Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom). Genes Dev. 2010;24:574–589. doi: 10.1101/gad.1898410 20203130

15. Nguyen AT, Zhang Y. The diverse functions of Dot1 and H3K79 methylation. Genes Dev. 2011;25:1345–1358. doi: 10.1101/gad.2057811 21724828

16. Frederiks F, Tzouros M, Oudgenoeg G, van Welsem T, Fornerod M, Krijgsveld J, et al. Nonprocessive methylation by Dot1 leads to functional redundancy of histone H3K79 methylation states. Nat Struct Mol Biol. 2008;15:550–557. doi: 10.1038/nsmb.1432 18511943

17. Mohan M, Lin C, Guest E, Shilatifard A. Licensed to elongate: a molecular mechanism for MLL-based leukaemogenesis. Nat Rev Cancer. 2010;10:721–728. doi: 10.1038/nrc2915 20844554

18. Ontoso D, Acosta I, van Leeuwen F, Freire R, San-Segundo PA. Dot1-dependent histone H3K79 methylation promotes activation of the Mek1 meiotic checkpoint effector kinase by regulating the Hop1 adaptor. PLoS Genetics. 2013;9:e1003262. doi: 10.1371/journal.pgen.1003262 23382701

19. Cecere G, Hoersch S, Jensen MB, Dixit S, Grishok A. The ZFP-1(AF10)/DOT-1 complex opposes H2B ubiquitination to reduce Pol II transcription. Mol Cell. 2013;50:894–907. doi: 10.1016/j.molcel.2013.06.002 23806335

20. Kim W, Choi M, Kim J-E. The histone methyltransferase Dot1/DOT1L as a critical regulator of the cell cycle. Cell Cycle. 2014;13:726–738. doi: 10.4161/cc.28104 24526115

21. San-Segundo PA, Roeder GS. Role for the silencing protein Dot1 in meiotic checkpoint control. Mol Biol Cell. 2000;11:3601–3615. doi: 10.1091/mbc.11.10.3601 11029058

22. Jones B, Su H, Bhat A, Lei H, Bajko J, Hevi S, et al. The histone H3K79 methyltransferase Dot1L is essential for mammalian development and heterochromatin structure. PLoS Genet. 2008;4:e1000190. doi: 10.1371/journal.pgen.1000190 18787701

23. Esse R, Gushchanskaia ES, Lord A, Grishok A. DOT1L complex suppresses transcription from enhancer elements and ectopic RNAi in Caenorhabditis elegans. RNA. 2019;25:1259–1273. doi: 10.1261/rna.070292.119 31300558

24. Ontoso D, Kauppi L, Keeney S, San-Segundo PA. Dynamics of DOT1L localization and H3K79 methylation during meiotic prophase I in mouse spermatocytes. Chromosoma. 2014;123:147–164. doi: 10.1007/s00412-013-0438-5 24105599

25. Shanower GA, Muller M, Blanton JL, Honti V, Gyurkovics H, Schedl P. Characterization of the grappa gene, the Drosophila histone H3 lysine 79 methyltransferase. Genetics. 2005;169:173–184. doi: 10.1534/genetics.104.033191 15371351

26. Min J, Feng Q, Li Z, Zhang Y, Xu R-M. Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase. Cell. 2003;112:711–723. doi: 10.1016/s0092-8674(03)00114-4 12628190

27. Esse R, Grishok A. Caenorhabditis elegans deficient in DOT-1.1 exhibit increases in H3K9me2 at enhancer and certain RNAi-Regulated regions. Cells. 2020;9:1846. doi: 10.3390/cells9081846 32781660

28. Kelly WG, Schaner CE, Dernburg AF, Lee M-H, Kim SK, Villeneuve AM, et al. X-chromosome silencing in the germline of C. elegans. Development. 2002;129:479–492. 11807039

29. Lui DY, Colaiácovo MP. Meiotic Development in Caenorhabditis elegans. In: Germ Cell Development in C. elegans. New York, NY: Springer New York; 2013. pp. 133–170. doi: 10.1007/978-1-4614-4015-4_6 22872477

30. Woglar A, Daryabeigi A, Adamo A, Habacher C, Machacek T, La Volpe A, et al. Matefin/SUN-1 phosphorylation is part of a surveillance mechanism to coordinate chromosome synapsis and recombination with meiotic progression and chromosome movement. PLoS Genet. 2013;9:e1003335. doi: 10.1371/journal.pgen.1003335 23505384

31. MacQueen AJ, Colaiácovo MP, McDonald K, Villeneuve AM. Synapsis-dependent and -independent mechanisms stabilize homolog pairing during meiotic prophase in C. elegans. Genes Dev. 2002;16:2428–2442. doi: 10.1101/gad.1011602 12231631

32. Phillips CM, Wong C, Bhalla N, Carlton PM, Weiser P, Meneely PM, et al. HIM-8 binds to the X chromosome pairing center and mediates chromosome-specific meiotic synapsis. Cell. 2005;123:1051–1063. doi: 10.1016/j.cell.2005.09.035 16360035

33. Smolikov S, Eizinger A, Schild-Prufert K, Hurlburt A, McDonald K, Engebrecht J, et al. SYP-3 restricts synaptonemal complex assembly to bridge paired chromosome axes during meiosis in Caenorhabditis elegans. Genetics. 2007;176:2015–2025. doi: 10.1534/genetics.107.072413 17565948

34. MacQueen AJ, Phillips CM, Bhalla N, Weiser P, Villeneuve AM, Dernburg AF. Chromosome sites play dual roles to establish homologous synapsis during meiosis in C. elegans. Cell. 2005;123:1037–1050. doi: 10.1016/j.cell.2005.09.034 16360034

35. Goodyer W, Kaitna S, Couteau F, Ward JD, Boulton SJ, Zetka M. HTP-3 links DSB formation with homolog pairing and crossing over during C. elegans meiosis. Dev Cell. 2008;14:263–274. doi: 10.1016/j.devcel.2007.11.016 18267094

36. Sung P. Catalysis of ATP-dependent homologous DNA pairing and strand exchange by yeast RAD51 protein. Science. 1994;265:1241–1243. doi: 10.1126/science.8066464 8066464

37. Colaiácovo MP, MacQueen AJ, Martinez-Perez E, McDonald K, Adamo A, La Volpe A, et al. Synaptonemal complex assembly in C. elegans is dispensable for loading strand-exchange proteins but critical for proper completion of recombination. Dev Cell. 2003;5:463–474. doi: 10.1016/s1534-5807(03)00232-6 12967565

38. Garcia-Muse T, Boulton SJ. Distinct modes of ATR activation after replication stress and DNA double-strand breaks in Caenorhabditis elegans. EMBO J. 2005;24:4345–4355. doi: 10.1038/sj.emboj.7600896 16319925

39. Mets DG, Meyer BJ. Condensins regulate meiotic DNA break distribution, thus crossover frequency, by controlling chromosome structure. Cell. 2009;139:73–86. doi: 10.1016/j.cell.2009.07.035 19781752

40. Meneely PM, Farago AF, Kauffman TM. Crossover distribution and high interference for both the X chromosome and an autosome during oogenesis and spermatogenesis in Caenorhabditis elegans. Genetics. 2002;162:1169–1177. 12454064

41. Jantsch V, Pasierbek P, Mueller MM, Schweizer D, Jantsch M, Loidl J. Targeted gene knockout reveals a role in meiotic recombination for ZHP-3, a Zip3-related protein in Caenorhabditis elegans. Mol Cell Biol. 2004;24:7998–8006. doi: 10.1128/MCB.24.18.7998-8006.2004 15340062

42. Reynolds A, Qiao H, Yang Y, Chen JK, Jackson N, Biswas K, et al. RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosis. Nature Genetics. 2013;45:269–278. doi: 10.1038/ng.2541 23396135

43. Singer MS, Kahana A, Wolf AJ, Meisinger LL, Peterson SE, Goggin C, et al. Identification of high-copy disruptors of telomeric silencing in Saccharomyces cerevisiae. Genetics. 1998;150:613–632. 9755194

44. Avgousti DC, Cecere G, Grishok A. The conserved PHD1-PHD2 domain of ZFP-1/AF10 is a discrete functional module essential for viability in Caenorhabditis elegans. Mol Cell Biol. 2013;33:999–1015. doi: 10.1128/MCB.01462-12 23263989

45. Bhalla N, Dernburg AF. A conserved checkpoint monitors meiotic chromosome synapsis in Caenorhabditis elegans. Science. 2005;310:1683–1686. doi: 10.1126/science.1117468 16339446

46. Kim Y, Kostow N, Dernburg AF. The chromosome axis mediates feedback control of CHK-2 to ensure crossover formation in C. elegans. Dev Cell. 2015;35:247–261. doi: 10.1016/j.devcel.2015.09.021 26506311

47. Deshong AJ, Ye AL, Lamelza P, Bhalla N. A quality control mechanism coordinates meiotic prophase events to promote crossover assurance. PLoS Genet. 2014;10:e1004291. doi: 10.1371/journal.pgen.1004291 24762417

48. Hodgkin J, Horvitz HR, Brenner S. Nondisjunction mutants of the nematode Caenorhabditis elegans. Genetics. 1979;91:67–94. 17248881

49. Gartner A, Milstein S, Ahmed S, Hodgkin J, Hengartner MO. A conserved checkpoint pathway mediates DNA damage-induced apoptosis and cell cycle arrest in C. elegans. Mol Cell. 2000;5:435–443. doi: 10.1016/s1097-2765(00)80438-4 10882129

50. Vlaming H, van Leeuwen F. The upstreams and downstreams of H3K79 methylation by DOT1L. Chromosoma. 2016;125:593–605. doi: 10.1007/s00412-015-0570-5 26728620

51. Zhu B, Chen S, Wang H, Yin C, Han C, Peng C, et al. The protective role of DOT1L in UV-induced melanomagenesis. Nat Commun. 2018;9:259. doi: 10.1038/s41467-017-02687-7 29343685

52. Okada Y, Feng Q, Lin Y, Jiang Q, Li Y, Coffield VM, et al. hDOT1L links histone methylation to leukemogenesis. Cell. 2005;121:167–178. doi: 10.1016/j.cell.2005.02.020 15851025

53. Deshpande AJ, Deshpande A, Sinha AU, Chen L, Chang J, Cihan A, et al. AF10 regulates progressive H3K79 methylation and HOX gene expression in diverse AML subtypes. Cancer Cell. 2014;26:896–908. doi: 10.1016/j.ccell.2014.10.009 25464900

54. Chen C-W, Koche RP, Sinha AU, Deshpande AJ, Zhu N, Eng R, et al. DOT1L inhibits SIRT1-mediated epigenetic silencing to maintain leukemic gene expression in MLL-rearranged leukemia. Nat Med. 2015;21:335–343. doi: 10.1038/nm.3832 25822366

55. Green RA, Kao H-L, Audhya A, Arur S, Mayers JR, Fridolfsson HN, et al. A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue. Cell. 2011;145:470–482. doi: 10.1016/j.cell.2011.03.037 21529718

56. Jenuwein T, Allis CD. Translating the histone code. Science. 2001;293: 1074–1080. doi: 10.1126/science.1063127 11498575

57. Turner BM. Cellular memory and the histone code. Cell. 2002;111:285–291. doi: 10.1016/s0092-8674(02)01080-2 12419240

58. Heng HH, Chamberlain JW, Shi XM, Spyropoulos B, Tsui LC, Moens PB. Regulation of meiotic chromatin loop size by chromosomal position. Proc Natl Acad Sci USA. 1996;93:2795–2800. doi: 10.1073/pnas.93.7.2795 8610120

59. Kauppi L, Barchi M, Baudat F, Romanienko PJ, Keeney S, Jasin M. Distinct properties of the XY pseudoautosomal region crucial for male meiosis. Science. 2011;331:916–920. doi: 10.1126/science.1195774 21330546

60. Gruhn JR, Rubio C, Broman KW, Hunt PA, Hassold T. Cytological studies of human meiosis: sex-specific differences in recombination originate at, or prior to, establishment of double-strand breaks. PLoS ONE. 2013;8:e85075. doi: 10.1371/journal.pone.0085075 24376867

61. Baier B, Hunt P, Broman KW, Hassold T. Variation in genome-wide levels of meiotic recombination is established at the onset of prophase in mammalian males. PLoS Genet. 2014;10:e1004125. doi: 10.1371/journal.pgen.1004125 24497841

62. Fingerman IM, Li H-C, Briggs SD. A charge-based interaction between histone H4 and Dot1 is required for H3K79 methylation and telomere silencing: identification of a new trans-histone pathway. Genes Dev. 2007;21:2018–2029. doi: 10.1101/gad.1560607 17675446

63. Altaf M, Utley RT, Lacoste N, Tan S, Briggs SD, Côté J. Interplay of chromatin modifiers on a short basic patch of histone H4 tail defines the boundary of telomeric heterochromatin. Mol Cell. 2007;28:1002–1014. doi: 10.1016/j.molcel.2007.12.002 18158898

64. Bani Ismail M, Shinohara M, Shinohara A. Dot1-dependent histone H3K79 methylation promotes the formation of meiotic double-strand breaks in the absence of histone H3K4 methylation in budding yeast. PLoS ONE. 2014;9:e96648. doi: 10.1371/journal.pone.0096648 24797370

65. Li Y, Wen H, Xi Y, Tanaka K, Wang H, Peng D, et al. AF9 YEATS domain links histone acetylation to DOT1L-mediated H3K79 methylation. Cell. 2014;159:558–571. doi: 10.1016/j.cell.2014.09.049 25417107

66. Chen S, Yang Z, Wilkinson AW, Deshpande AJ, Sidoli S, Krajewski K, et al. The PZP domain of AF10 senses unmodified H3K27 to regulate DOT1L-mediated methylation of H3K79. Mol Cell. 2015;60: 319–327. doi: 10.1016/j.molcel.2015.08.019 26439302

67. Dernburg AF, McDonald K, Moulder G, Barstead R, Dresser M, Villeneuve AM. Meiotic Recombination in C. elegans initiates by a conserved mechanism and is dispensable for homologous chromosome synapsis. Cell. 1998;94:387–398. doi: 10.1016/s0092-8674(00)81481-6 9708740

68. MacQueen AJ, Villeneuve AM. Nuclear reorganization and homologous chromosome pairing during meiotic prophase require C. elegans chk-2. Genes Dev. 2001;15:1674–1687. doi: 10.1101/gad.902601 11445542

69. San-Segundo PA, Roeder GS. Pch2 links chromatin silencing to meiotic checkpoint control. Cell. 1999;97: 313–324. doi: 10.1016/s0092-8674(00)80741-2 10319812

70. Herruzo E, Ontoso D, González-Arranz S, Cavero S, Lechuga A, San-Segundo PA. The Pch2 AAA+ ATPase promotes phosphorylation of the Hop1 meiotic checkpoint adaptor in response to synaptonemal complex defects. Nucleic Acids Res. 2016;44:7722–7741. doi: 10.1093/nar/gkw506 27257060

71. Herruzo E, Santos B, Freire R, Carballo JA, San-Segundo PA. Characterization of Pch2 localization determinants reveals a nucleolar-independent role in the meiotic recombination checkpoint. Chromosoma. 2019;128:297–316. doi: 10.1007/s00412-019-00696-7 30859296

72. Huyen Y, Zgheib O, Ditullio RA, Gorgoulis VG, Zacharatos P, Petty TJ, et al. Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature. 2004;432:406–411. doi: 10.1038/nature03114 15525939

73. Botuyan MV, Lee J, Ward IM, Kim J-E, Thompson JR, Chen J, et al. Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell. 2006;127:1361–1373. doi: 10.1016/j.cell.2006.10.043 17190600

74. Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974;77: 71–94. 4366476

75. Thompson O, Edgley M, Strasbourger P, Flibotte S, Ewing B, Adair R, et al. The million mutation project: a new approach to genetics in Caenorhabditis elegans. Genome Res. 2013;23:1749–1762. doi: 10.1101/gr.157651.113 23800452

76. Nadarajan S, Lambert TJ, Altendorfer E, Gao J, Blower MD, Waters JC, et al. Polo-like kinase-dependent phosphorylation of the synaptonemal complex protein SYP-4 regulates double-strand break formation through a negative feedback loop. eLife. 2017;6:e23437. doi: 10.7554/eLife.23437 28346135

77. Bhalla N, Wynne DJ, Jantsch V, Dernburg AF. ZHP-3 acts at crossovers to couple meiotic recombination with synaptonemal complex disassembly and bivalent formation in C. elegans. PLoS Genet. 2008;4:e1000235. doi: 10.1371/journal.pgen.1000235 18949042

78. Villeneuve AM. A cis-acting locus that promotes crossing over between X chromosomes in Caenorhabditis elegans. Genetics. 1994;136:887–902. 8005443

79. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9:676–682. doi: 10.1038/nmeth.2019 22743772

80. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9: 671–675. doi: 10.1038/nmeth.2089 22930834

81. Kelly KO, Dernburg AF, Stanfield GM, Villeneuve AM. Caenorhabditis elegans msh-5 is required for both normal and radiation-induced meiotic crossing over but not for completion of meiosis. Genetics. 2000;156:617–630. 11014811

82. Mansisidor AR, Cecere G, Hoersch S, Jensen MB, Kawli T, Kennedy LM, et al. A conserved PHD finger protein and endogenous RNAi modulate insulin signaling in Caenorhabditis elegans. PLoS Genet. 2011;7:e1002299. doi: 10.1371/journal.pgen.1002299 21980302


Článek vyšel v časopise

PLOS Genetics


2020 Číslo 10

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Antiseptika a prevence ve stomatologii
nový kurz
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Diagnostika a léčba deprese pro ambulantní praxi
Autoři: MUDr. Jan Hubeňák, Ph.D

Snímatelné zubní náhrady a fixační krémy
Autoři: doc. MUDr. Hana Hubálková, Ph.D.

Nová éra v léčbě migrény
Autoři: MUDr. Eva Medová, MUDr. Tomáš Nežádal, Ph.D.

Význam nutraceutik u kardiovaskulárních onemocnění
Autoři:

Všechny kurzy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se