Substitutions in the Amino-Terminal Tail of Neurospora Histone H3 Have Varied Effects on DNA Methylation
Eukaryotic genomes are partitioned into active and inactive domains called euchromatin and heterochromatin, respectively. In Neurospora crassa, heterochromatin formation requires methylation of histone H3 at lysine 9 (H3K9) by the SET domain protein DIM-5. Heterochromatin protein 1 (HP1) reads this mark and directly recruits the DNA methyltransferase, DIM-2. An ectopic H3 gene carrying a substitution at K9 (hH3K9L or hH3K9R) causes global loss of DNA methylation in the presence of wild-type hH3 (hH3WT). We investigated whether other residues in the N-terminal tail of H3 are important for methylation of DNA and of H3K9. Mutations in the N-terminal tail of H3 were generated and tested for effects in vitro and in vivo, in the presence or absence of the wild-type allele. Substitutions at K4, K9, T11, G12, G13, K14, K27, S28, and K36 were lethal in the absence of a wild-type allele. In contrast, mutants bearing substitutions of R2, A7, R8, S10, A15, P16, R17, K18, and K23 were viable. The effect of substitutions on DNA methylation were variable; some were recessive and others caused a semi-dominant loss of DNA methylation. Substitutions of R2, A7, R8, S10, T11, G12, G13, K14, and P16 caused partial or complete loss of DNA methylation in vivo. Only residues R8-G12 were required for DIM-5 activity in vitro. DIM-5 activity was inhibited by dimethylation of H3K4 and by phosphorylation of H3S10, but not by acetylation of H3K14. We conclude that the H3 tail acts as an integrating platform for signals that influence DNA methylation, in part through methylation of H3K9.
Vyšlo v časopise:
Substitutions in the Amino-Terminal Tail of Neurospora Histone H3 Have Varied Effects on DNA Methylation. PLoS Genet 7(12): e32767. doi:10.1371/journal.pgen.1002423
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002423
Souhrn
Eukaryotic genomes are partitioned into active and inactive domains called euchromatin and heterochromatin, respectively. In Neurospora crassa, heterochromatin formation requires methylation of histone H3 at lysine 9 (H3K9) by the SET domain protein DIM-5. Heterochromatin protein 1 (HP1) reads this mark and directly recruits the DNA methyltransferase, DIM-2. An ectopic H3 gene carrying a substitution at K9 (hH3K9L or hH3K9R) causes global loss of DNA methylation in the presence of wild-type hH3 (hH3WT). We investigated whether other residues in the N-terminal tail of H3 are important for methylation of DNA and of H3K9. Mutations in the N-terminal tail of H3 were generated and tested for effects in vitro and in vivo, in the presence or absence of the wild-type allele. Substitutions at K4, K9, T11, G12, G13, K14, K27, S28, and K36 were lethal in the absence of a wild-type allele. In contrast, mutants bearing substitutions of R2, A7, R8, S10, A15, P16, R17, K18, and K23 were viable. The effect of substitutions on DNA methylation were variable; some were recessive and others caused a semi-dominant loss of DNA methylation. Substitutions of R2, A7, R8, S10, T11, G12, G13, K14, and P16 caused partial or complete loss of DNA methylation in vivo. Only residues R8-G12 were required for DIM-5 activity in vitro. DIM-5 activity was inhibited by dimethylation of H3K4 and by phosphorylation of H3S10, but not by acetylation of H3K14. We conclude that the H3 tail acts as an integrating platform for signals that influence DNA methylation, in part through methylation of H3K9.
Zdroje
1. CamposEReinbergDanny 2009 Histones: Annotating Chromatin. Annu Rev Genet 43
2. MalikHSHenikoffS 2003 Phylogenomics of the nucleosome. Nat Struct Biol 10 882 891
3. WoudtLPPastinkAKempers-VeenstraAEJansenAEMagerWH 1983 The genes coding for histone H3 and H4 in Neurospora crassa are unique and contain intervening sequences. Nucleic Acids Res 11 5347 5360
4. HaysSMSwansonJSelkerEU 2002 Identification and characterization of the genes encoding the core histones and histone variants of Neurospora crassa. Genetics 160 961 973
5. SmithMMSantistebanMS 1998 Genetic dissection of histone function. Methods 15 269 281
6. NakanishiSSandersonBWDelventhalKMBradfordWDStaehling-HamptonK 2008 A comprehensive library of histone mutants identifies nucleosomal residues required for H3K4 methylation. Nat Struct Mol Biol 15 881 888
7. DaiJHylandEMYuanDSHuangHBaderJS 2008 Probing nucleosome function: a highly versatile library of synthetic histone H3 and H4 mutants. Cell 134 1066 1078
8. MatsubaraKSanoNUmeharaTHorikoshiM 2007 Global analysis of functional surfaces of core histones with comprehensive point mutants. Genes Cells 12 13 33
9. MelloneBGBallLSukaNGrunsteinMRPartridgeJF 2003 Centromere silencing and function in fission yeast is governed by the amino terminus of histone H3. Curr Biol 13 1748 1757
10. KouzaridesT 2007 Chromatin modifications and their function. Cell 128 693 705
11. LucoRFPanQTominagaKBlencoweBJPereira-SmithOM 2010 Regulation of alternative splicing by histone modifications. Science 327 996 1000
12. MegeePCMorganBAMittmanBASmithMM 1990 Genetic analysis of histone H4: essential role of lysines subject to reversible acetylation. Science 247 841 845
13. XiongLAdhvaryuKKSelkerEUWangY 2010 Mapping of lysine methylation and acetylation in core histones of Neurospora crassa. Biochemistry 49 5236 5243
14. TamaruHSelkerEU 2001 A histone H3 methyltransferase controls DNA methylation in Neurospora crassa. Nature 414 277 283
15. TamaruHZhangXMcMillenDSinghPBNakayamaJ 2003 Trimethylated lysine 9 of histone H3 is a mark for DNA methylation in Neurospora crassa. Nat Genet 34 75 79
16. SelkerEU 1990 Premeiotic instability of repeated sequences in Neurospora crassa. Annu Rev Genet 24 579 613
17. GalaganJESelkerEU 2004 RIP: the evolutionary cost of genome defense. Trends Genet 20 417 423
18. SelkerEUTountasNACrossSHMargolinBSMurphyJG 2003 The methylated component of the Neurospora crassa genome. Nature 422 893 897
19. LewisZAHondaSKhlafallahTKJeffressJKFreitagM 2009 Relics of repeat-induced point mutation direct heterochromatin formation in Neurospora crassa. Genome Res 19 427 437
20. FreitagMHickeyPCKhlafallahTKReadNDSelkerEU 2004 HP1 is essential for DNA methylation in Neurospora. Mol Cell 13 427 434
21. HondaSSelkerEU 2008 Direct interaction between DNA methyltransferase DIM-2 and HP1 is required for DNA methylation in Neurospora. Mol Cell Biol 28 6044 6055
22. KouzminovaEASelkerEU 2001 Dim-2 encodes a DNA-methyltransferase responsible for all known cytosine methylation in Neurospora. EMBO Journal 20 4309 4323
23. LachnerMO'CarrollDReaSMechtlerKJenuweinT 2001 Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410 116 120
24. JacobsSATavernaSDZhangYBriggsSDLiJ 2001 Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3. Embo J 20 5232 5241
25. LewisZAAdhvaryuKKHondaSShiverALSelkerEU 2010 Identification of DIM-7, a protein required to target the DIM-5 H3 methyltransferase to chromatin. Proc Natl Acad Sci U S A
26. LewisZAAdhvaryuKKHondaSShiverALKnipM 2010 DNA Methylation and Normal Chromosome Behavior in Neurospora Depend on Five Components of a Histone Methyltransferase Complex, DCDC. PLoS Genet 6 e1001196 doi:10.1371/journal.pgen.1001196
27. JacobsSAKhorasanizadehS 2002 Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail. Science 295 2080 2083
28. AdhvaryuKKSelkerEU 2008 Protein phosphatase PP1 is required for normal DNA methylation in Neurospora. Genes Dev 22 3391 3396
29. EbbsMLBenderJ 2006 Locus-specific control of DNA methylation by the Arabidopsis SUVH5 histone methyltransferase. Plant Cell 18 1166 1176
30. JacksonJPLindrothAMCaoXJacobsenSE 2002 Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase. Nature 416 556 560
31. JacksonJPJohnsonLJasencakovaZZhangXPerezBurgosL 2004 Dimethylation of histone H3 lysine 9 is a critical mark for DNA methylation and gene silencing in Arabidopsis thaliana. Chromosoma 112 308 315
32. LehnertzBUedaYDerijckAABraunschweigUPerez-BurgosL 2003 Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol 13 1192 1200
33. ZhangXYangZKhanSIHortonJRTamaruH 2003 Structural basis for the product specificity of histone lysine methyltransferases. Mol Cell 12 177 185
34. IrelanJTSelkerEU 1997 Cytosine methylation associated with repeat-induced point mutation causes epigenetic gene silencing in Neurospora crassa. Genetics 146 509 523
35. ReaSEisenhaberFO'CarrollDStrahlBDSunZW 2000 Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406 593 599
36. NakayamaJRiceJCStrahlBDAllisCDGrewalSI 2001 Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 292 110 113
37. SchultzDCAyyanathanKNegorevDMaulGGRauscherFJ3rd 2002 SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev 16 919 932
38. SmithKMDobosyJRReifsnyderJERountreeMRAndersonDC 2010 H2B- and H3-specific Histone Deacetylases are Required for DNA Methylation in Neurospora crassa. Genetics
39. CanzioDChangEYShankarSKuchenbeckerKMSimonMD 2011 Chromodomain-mediated oligomerization of HP1 suggests a nucleosome-bridging mechanism for heterochromatin assembly. Mol Cell 41 67 81
40. XhemalceBKouzaridesT 2010 A chromodomain switch mediated by histone H3 Lys 4 acetylation regulates heterochromatin assembly. Genes Dev 24 647 652
41. Casas-MollanoJAJeongBRXuJMoriyamaHCeruttiH 2008 The MUT9p kinase phosphorylates histone H3 threonine 3 and is necessary for heritable epigenetic silencing in Chlamydomonas. Proc Natl Acad Sci U S A 105 6486 6491
42. ShimadaMNiidaHZineldeenDHTagamiHTanakaM 2008 Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-induced transcriptional repression. Cell 132 221 232
43. MetzgerEYinNWissmannMKunowskaNFischerK 2008 Phosphorylation of histone H3 at threonine 11 establishes a novel chromatin mark for transcriptional regulation. Nat Cell Biol 10 53 60
44. DunnKLDavieJR 2005 Stimulation of the Ras-MAPK pathway leads to independent phosphorylation of histone H3 on serine 10 and 28. Oncogene 24 3492 3502
45. MetzgerEImhofAPatelDKahlPHoffmeyerK 2010 Phosphorylation of histone H3T6 by PKCbeta(I) controls demethylation at histone H3K4. Nature 464 792 796
46. KellyAEGhenoiuCXueJZZierhutCKimuraH 2010 Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B. Science 330 235 239
47. WangFDaiJDaumJRNiedzialkowskaEBanerjeeB 2010 Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis. Science 330 231 235
48. HoubenADemidovDRuttenTScheidtmannKH 2005 Novel phosphorylation of histone H3 at threonine 11 that temporally correlates with condensation of mitotic and meiotic chromosomes in plant cells. Cytogenet Genome Res 109 148 155
49. RathertPZhangXFreundCChengXJeltschA 2008 Analysis of the substrate specificity of the Dim-5 histone lysine methyltransferase using peptide arrays. Chem Biol 15 5 11
50. YamadaTFischleWSugiyamaTAllisCDGrewalSI 2005 The nucleation and maintenance of heterochromatin by a histone deacetylase in fission yeast. Mol Cell 20 173 185
51. ChenESZhangKNicolasECamHPZofallM 2008 Cell cycle control of centromeric repeat transcription and heterochromatin assembly. Nature 451 734 737
52. ZhangKMoschKFischleWGrewalSI 2008 Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin. Nat Struct Mol Biol 15 381 388
53. NicolasEYamadaTCamHPFitzgeraldPCKobayashiR 2007 Distinct roles of HDAC complexes in promoter silencing, antisense suppression and DNA damage protection. Nat Struct Mol Biol 14 372 380
54. MotamediMRHongEJLiXGerberSDenisonC 2008 HP1 proteins form distinct complexes and mediate heterochromatic gene silencing by nonoverlapping mechanisms. Mol Cell 32 778 790
55. SugiyamaTCamHPSugiyamaRNomaKZofallM 2007 SHREC, an effector complex for heterochromatic transcriptional silencing. Cell 128 491 504
56. BedfordMTClarkeSG 2009 Protein arginine methylation in mammals: who, what, and why. Mol Cell 33 1 13
57. KirmizisASantos-RosaHPenkettCJSingerMAVermeulenM 2007 Arginine methylation at histone H3R2 controls deposition of H3K4 trimethylation. Nature 449 928 932
58. GuccioneEBassiCCasadioFMartinatoFCesaroniM 2007 Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusive. Nature 449 933 937
59. KirmizisASantos-RosaHPenkettCJSingerMAGreenRD 2009 Distinct transcriptional outputs associated with mono- and dimethylated histone H3 arginine 2. Nat Struct Mol Biol 16 449 451
60. ChinHGPradhanMEstevePOPatnaikDEvansTCJr 2005 Sequence specificity and role of proximal amino acids of the histone H3 tail on catalysis of murine G9A lysine 9 histone H3 methyltransferase. Biochemistry 44 12998 13006
61. EskelandRCzerminBBoekeJBonaldiTRegulaJT 2004 The N-terminus of Drosophila SU(VAR)3-9 mediates dimerization and regulates its methyltransferase activity. Biochemistry 43 3740 3749
62. RudolphTYonezawaMLeinSHeidrichKKubicekS 2007 Heterochromatin formation in Drosophila is initiated through active removal of H3K4 methylation by the LSD1 homolog SU(VAR)3-3. Mol Cell 26 103 115
63. LiFHuarteMZaratieguiMVaughnMWShiY 2008 Lid2 is required for coordinating H3K4 and H3K9 methylation of heterochromatin and euchromatin. Cell 135 272 283
64. OoiSKTQiuCBernsteinELiKJiaD 2007 DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 448 714 717
65. ButlerJSLeeJHSkalnikDG 2008 CFP1 interacts with DNMT1 independently of association with the Setd1 Histone H3K4 methyltransferase complexes. DNA Cell Biol 27 533 543
66. ThomsonJPSkenePJSelfridgeJClouaireTGuyJ 2010 CpG islands influence chromatin structure via the CpG-binding protein Cfp1. Nature 464 1082 1086
67. DavisRHDe SerresFJ 1970 Genetic and microbiological research techniques for Neurospora crassa. Meth Enzymol 17A 47 143
68. PerkinsDD 1986 Hints and precautions for the care, feeding and breeding of Neurospora. Fungal Genetics Newsl 33 35 41
69. DavisRH 2000 Neurospora: Contributions of a Model Organism Oxford University Press 333
70. IrelanJMiaoVSelkerEU 1993 Small scale DNA preps for Neurospora crassa. Fungal Genetics Newsletter 40 24
71. OakleyBRRinehartJEMitchellBLOakleyCECarmonaC 1987 Cloning, mapping and molecular analysis of the pyrG (orotidine- 5′-phosphate decarboxylase) gene of Aspergillus nidulans. Gene 61 385 399
72. SouthernEM 1975 Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98 503 517
73. FeinbergAPVogelsteinB 1983 A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity (I). Anal Biochem 132 6 13
74. SelkerEUStevensJN 1987 Signal for DNA methylation associated with tandem duplication in Neurospora crassa. Mol Cell Biol 7 1032 1038
75. ZhangXTamaruHKhanSHortonJKeefeL 2002 Structure of the Neurospora SET Domain Protein DIM-5, a Histone H3 Lysine Methyltransferase. Cell 111 117 127
76. BaumJAGilesNH 1986 DNase I hypersensitive sites within the inducible qa gene cluster of Neurospora crassa. Proc Natl Acad Sci U S A 83 6533 6537
77. TurnerBM 2005 Reading signals on the nucleosome with a new nomenclature for modified histones. Nat Struct Mol Biol 12 110 112
78. HickeyPCJacobsonDReadNDLouise GlassNL 2002 Live-cell imaging of vegetative hyphal fusion in Neurospora crassa. Fungal Genet Biol 37 109 119
79. AbramoffMDMagelhaesPJRamSJ 2004 Image Processing with ImageJ. Biophotonics International 11 36 42
80. NelsonCJSantos-RosaHKouzaridesT 2006 Proline isomerization of histone H3 regulates lysine methylation and gene expression. Cell 126 905 916
81. DuncanEMMuratore-SchroederTLCookRGGarciaBAShabanowitzJ 2008 Cathepsin L proteolytically processes histone H3 during mouse embryonic stem cell differentiation. Cell 135 284 294
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