The DNA Polymerase δ Has a Role in the Deposition of Transcriptionally Active Epigenetic Marks, Development and Flowering

English version České info

Three DNA polymerases replicate DNA in Eukaryotes. DNA polymerase α (Polα) initiates strand synthesis, which is performed by Polε and Polδ in leading and lagging strands, respectively. Not only the information encoded in the DNA, but also the inheritance of chromatin states is essential during development. Loss of function mutants in DNA polymerases lead to lethal phenotypes. Hence, hypomorphic alleles are necessary to study their roles beyond DNA replication. Here we identify a thermosensitive mutant of the Polδ in the model plant Arabidopsis thaliana, which bears an aminoacid substitution in the polymerase-domain. The mutants were essentially normal at 18°C but arrested development at 28°C. Interestingly, at 24°C we were able to study the roles of Polδ in epigenetic inheritance and plant development. We observed a tight connection between DNA replication stress and an increase the deposition of transcriptionally active chromatin marks in the SEPALLATA3 (SEP3) locus. Finally, we tested by genetic means that the ectopic expression of SEP3 was indeed the cause of early flowering and the leaf phenotypes by promoting the expression of FLOWERING LOCUS T (FT). These results link Polδ activity to the proper establishment of transcriptionally active epigenetic marks, which then impact the development of multicellular organisms.

Vyšlo v časopise: The DNA Polymerase δ Has a Role in the Deposition of Transcriptionally Active Epigenetic Marks, Development and Flowering. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004975
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004975

Souhrn

Zdroje

1. Corbesier L, Vincent C, Jang S, Fornara F, Fan Q, et al. (2007) FT protein movement contributes to long-distance signaling in floral induction of Arabidopsis. Science 316: 1030–1033. 17446353

2. Jaeger KE, Wigge PA (2007) FT protein acts as a long-range signal in Arabidopsis. Curr Biol 17: 1050–1054. 17540569

3. Mathieu J, Warthmann N, Kuttner F, Schmid M (2007) Export of FT protein from phloem companion cells is sufficient for floral induction in Arabidopsis. Curr Biol 17: 1055–1060. 17540570

4. Kim DH, Doyle MR, Sung S, Amasino RM (2009) Vernalization: winter and the timing of flowering in plants. Annu Rev Cell Dev Biol 25: 277–299. doi: 10.1146/annurev.cellbio.042308.113411 19575660

5. Andres F, Coupland G (2012) The genetic basis of flowering responses to seasonal cues. Nat Rev Genet 13: 627–639. doi: 10.1038/nrg3291 22898651

6. Adrian J, Farrona S, Reimer JJ, Albani MC, Coupland G, et al. (2010) cis-Regulatory elements and chromatin state coordinately control temporal and spatial expression of FLOWERING LOCUS T in Arabidopsis. Plant Cell 22: 1425–1440. doi: 10.1105/tpc.110.074682 20472817

7. Farrona S, Thorpe FL, Engelhorn J, Adrian J, Dong X, et al. (2011) Tissue-specific expression of FLOWERING LOCUS T in Arabidopsis is maintained independently of polycomb group protein repression. Plant Cell 23: 3204–3214. doi: 10.1105/tpc.111.087809 21917549

8. Jeong JH, Song HR, Ko JH, Jeong YM, Kwon YE, et al. (2009) Repression of FLOWERING LOCUS T chromatin by functionally redundant histone H3 lysine 4 demethylases in Arabidopsis. PloS One 4: e8033. doi: 10.1371/journal.pone.0008033 19946624

9. Jiang D, Wang Y, He Y (2008) Repression of FLOWERING LOCUS C and FLOWERING LOCUS T by the Arabidopsis Polycomb repressive complex 2 components. PloS One 3: e3404. doi: 10.1371/journal.pone.0003404 18852898

10. Wang Y, Gu X, Yuan W, Schmitz RJ, He Y (2014) Photoperiodic Control of the Floral Transition through a Distinct Polycomb Repressive Complex. Dev Cell 28: 727–736. doi: 10.1016/j.devcel.2014.01.029 24613395

11. Barrero JM, Gonzalez-Bayon R, del Pozo JC, Ponce MR, Micol JL (2007) INCURVATA2 encodes the catalytic subunit of DNA Polymerase alpha and interacts with genes involved in chromatin-mediated cellular memory in Arabidopsis thaliana. Plant Cell 19: 2822–2838. 17873092

12. Goodrich J, Puangsomlee P, Martin M, Long D, Meyerowitz EM, et al. (1997) A Polycomb-group gene regulates homeotic gene expression in Arabidopsis. Nature 386: 44–51. 9052779

13. Kotake T, Takada S, Nakahigashi K, Ohto M, Goto K (2003) Arabidopsis TERMINAL FLOWER 2 gene encodes a heterochromatin protein 1 homolog and represses both FLOWERING LOCUS T to regulate flowering time and several floral homeotic genes. Plant Cell Physiol 44: 555–564. 12826620

14. Burgers PM (2009) Polymerase dynamics at the eukaryotic DNA replication fork. J Biol Chem 284: 4041–4045. doi: 10.1074/jbc.R800062200 18835809

15. Li F, Martienssen R, Cande WZ (2011) Coordination of DNA replication and histone modification by the Rik1-Dos2 complex. Nature 475: 244–248. doi: 10.1038/nature10161 21725325

16. del Olmo I, Lopez-Gonzalez L, Martin-Trillo MM, Martinez-Zapater JM, Pineiro M, et al. (2010) EARLY IN SHORT DAYS 7 (ESD7) encodes the catalytic subunit of DNA polymerase epsilon and is required for flowering repression through a mechanism involving epigenetic gene silencing. Plant J 61: 623–636. doi: 10.1111/j.1365-313X.2009.04093.x 19947980

17. Hyun Y, Yun H, Park K, Ohr H, Lee O, et al. (2013) The catalytic subunit of Arabidopsis DNA polymerase alpha ensures stable maintenance of histone modification. Development 140: 156–166. doi: 10.1242/dev.084624 23154417

18. Liu J, Ren X, Yin H, Wang Y, Xia R, et al. (2010) Mutation in the catalytic subunit of DNA polymerase alpha influences transcriptional gene silencing and homologous recombination in Arabidopsis. Plant J 61: 36–45. doi: 10.1111/j.1365-313X.2009.04026.x 19769574

19. Yin H, Zhang X, Liu J, Wang Y, He J, et al. (2009) Epigenetic regulation, somatic homologous recombination, and abscisic acid signaling are influenced by DNA polymerase epsilon mutation in Arabidopsis. Plant Cell 21: 386–402. doi: 10.1105/tpc.108.061549 19244142

20. Branzei D, Foiani M (2010) Maintaining genome stability at the replication fork. Nat Rev Mol Cell Biol 11: 208–219. doi: 10.1038/nrm2852 20177396

21. Prindle MJ, Loeb LA (2012) DNA polymerase delta in DNA replication and genome maintenance. Env Mol Mutag 53: 666–682.

22. Schuermann D, Molinier J, Fritsch O, Hohn B (2005) The dual nature of homologous recombination in plants. Trends Genet 21: 172–181. 15734576

23. Palles C, Cazier JB, Howarth KM, Domingo E, Jones AM, et al. (2013) Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet 45: 136–144. doi: 10.1038/ng.2503 23263490

24. Jenik PD, Jurkuta RE, Barton MK (2005) Interactions between the cell cycle and embryonic patterning in Arabidopsis uncovered by a mutation in DNA polymerase epsilon. Plant Cell 17: 3362–3377. 16278345

25. Ronceret A, Guilleminot J, Lincker F, Gadea-Vacas J, Delorme V, et al. (2005) Genetic analysis of two Arabidopsis DNA polymerase epsilon subunits during early embryogenesis. Plant J 44: 223–236. 16212602

26. Jander G, Norris SR, Rounsley SD, Bush DF, Levin IM, et al. (2002) Arabidopsis map-based cloning in the post-genome era. Plant Physiol 129: 440–450. 12068090

27. Swan MK, Johnson RE, Prakash L, Prakash S, Aggarwal AK (2009) Structural basis of high-fidelity DNA synthesis by yeast DNA polymerase delta. Nat Struct & Mol Biol 16: 979–986. doi: 10.1038/nsmb.2941 25580578

28. Mullins JG (2012) Structural modelling pipelines in next generation sequencing projects. Adv Protein Chem Struct Biol 89: 117–167. doi: 10.1016/B978-0-12-394287-6.00005-7 23046884

29. Rothwell PJ, Waksman G (2005) Structure and mechanism of DNA polymerases. Adv Protein Chem 71: 401–440. 16230118

30. Petsko GA, Ringe D (2004) Protein Structure and Function: New Science Press. 25057686

31. Schuermann D, Fritsch O, Lucht JM, Hohn B (2009) Replication stress leads to genome instabilities in Arabidopsis DNA polymerase delta mutants. Plant Cell 21: 2700–2714. doi: 10.1105/tpc.109.069682 19789281

32. Colon-Carmona A, You R, Haimovitch-Gal T, Doerner P (1999) Technical advance: spatio-temporal analysis of mitotic activity with a labile cyclin-GUS fusion protein. Plant J 20: 503–508. 10607302

33. Blazquez MA, Ahn JH, Weigel D (2003) A thermosensory pathway controlling flowering time in Arabidopsis thaliana. Nat Genet 33: 168–171. 12548286

34. Yoo SK, Chung KS, Kim J, Lee JH, Hong SM, et al. (2005) CONSTANS activates SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 through FLOWERING LOCUS T to promote flowering in Arabidopsis. Plant Physiol 139: 770–778. 16183837

35. Teper-Bamnolker P, Samach A (2005) The flowering integrator FT regulates SEPALLATA3 and FRUITFULL accumulation in Arabidopsis leaves. Plant Cell 17: 2661–2675. 16155177

36. Castillejo C, Romera-Branchat M, Pelaz S (2005) A new role of the Arabidopsis SEPALLATA3 gene revealed by its constitutive expression. Plant J 43: 586–596. 16098111

37. Honma T, Goto K (2001) Complexes of MADS-box proteins are sufficient to convert leaves into floral organs. Nature 409: 525–529. 11206550

38. Lopez-Vernaza M, Yang S, Muller R, Thorpe F, de Leau E, et al. (2012) Antagonistic roles of SEPALLATA3, FT and FLC genes as targets of the polycomb group gene CURLY LEAF. PloS One 7: e30715. doi: 10.1371/journal.pone.0030715 22363474

39. Hwan Lee J, Joon Kim J, Ahn JH (2012) Role of SEPALLATA3 (SEP3) as a downstream gene of miR156-SPL3-FT circuitry in ambient temperature-responsive flowering. Plant Signal Behav 7: 1151–1154. doi: 10.4161/psb.21366 22899051

40. Liu C, Xi W, Shen L, Tan C, Yu H (2009) Regulation of floral patterning by flowering time genes. Dev Cell 16: 711–722. doi: 10.1016/j.devcel.2009.03.011 19460347

41. Kim JM, To TK, Ishida J, Matsui A, Kimura H, et al. (2012) Transition of chromatin status during the process of recovery from drought stress in Arabidopsis thaliana. Plant Cell Physiol 53: 847–856. doi: 10.1093/pcp/pcs053 22505693

42. Kumar SV, Wigge PA (2010) H2A.Z-containing nucleosomes mediate the thermosensory response in Arabidopsis. Cell 140: 136–147. doi: 10.1016/j.cell.2009.11.006 20079334

43. Liu C, Zhou J, Bracha-Drori K, Yalovsky S, Ito T, et al. (2007) Specification of Arabidopsis floral meristem identity by repression of flowering time genes. Development 134: 1901–1910. 17428825

44. Ding Y, Fromm M, Avramova Z (2012) Multiple exposures to drought ‘train’ transcriptional responses in Arabidopsis. Nat Comm 3: 740.

45. Muramoto T, Muller I, Thomas G, Melvin A, Chubb JR (2010) Methylation of H3K4 Is required for inheritance of active transcriptional states. Curr Biol 20: 397–406. doi: 10.1016/j.cub.2010.01.017 20188556

46. Smith DJ, Whitehouse I (2012) Intrinsic coupling of lagging-strand synthesis to chromatin assembly. Nature 483: 434–438. doi: 10.1038/nature10895 22419157

47. Turck F, Roudier F, Farrona S, Martin-Magniette ML, Guillaume E, et al. (2007) Arabidopsis TFL2/LHP1 specifically associates with genes marked by trimethylation of histone H3 lysine 27. PLoS Genet 3: e86. 17542647

48. Zhang X, Germann S, Blus BJ, Khorasanizadeh S, Gaudin V, et al. (2007) The Arabidopsis LHP1 protein colocalizes with histone H3 Lys27 trimethylation. Nat Struct & Mol Biol 14: 869–871. doi: 10.1038/nsmb.2941 25580578

49. Weedon MN, Ellard S, Prindle MJ, Caswell R, Lango Allen H, et al. (2013) An in-frame deletion at the polymerase active site of POLD1 causes a multisystem disorder with lipodystrophy. Nat Genet 45: 947–950. doi: 10.1038/ng.2670 23770608

50. Yamaguchi A, Kobayashi Y, Goto K, Abe M, Araki T (2005) TWIN SISTER OF FT (TSF) acts as a floral pathway integrator redundantly with FT. Plant Cell Physiol 46: 1175–1189. 15951566

51. Alonso JM, Stepanova AN, Leisse TJ, Kim CJ, Chen H, et al. (2003) Genome-wide insertional mutagenesis of Arabidopsis thaliana. Science 301: 653–657. 12893945

52. Balasubramanian S, Sureshkumar S, Lempe J, Weigel D (2006) Potent induction of Arabidopsis thaliana flowering by elevated growth temperature. PLoS Genet 2: e106. 16839183

53. Redei GP (1962) Supervital Mutants of Arabidopsis. Genetics 47: 443–460. 17248096

54. Strasser B, Alvarez MJ, Califano A, Cerdan PD (2009) A complementary role for ELF3 and TFL1 in the regulation of flowering time by ambient temperature. Plant J 58: 629–640. doi: 10.1111/j.1365-313X.2009.03811.x 19187043

55. Page T, Macknight R, Yang CH, Dean C (1999) Genetic interactions of the Arabidopsis flowering time gene FCA, with genes regulating floral initiation. Plant J 17: 231–239. 10097382

56. Ausin I, Alonso-Blanco C, Jarillo JA, Ruiz-Garcia L, Martinez-Zapater JM (2004) Regulation of flowering time by FVE, a retinoblastoma-associated protein. Nat Genet 36: 162–166. 14745447

57. Gherbi H, Gallego ME, Jalut N, Lucht JM, Hohn B, et al. (2001) Homologous recombination in planta is stimulated in the absence of Rad50. EMBO Rep 2: 287–291. 11306548

58. Swoboda P, Gal S, Hohn B, Puchta H (1994) Intrachromosomal homologous recombination in whole plants. EMBO J 13: 484–489. 8313893

59. Jander G (2006) Gene identification and cloning by molecular marker mapping. Methods Mol Biol 323: 115–126. 16739572

60. Hajdukiewicz P, Svab Z, Maliga P (1994) The small, versatile pPZP family of Agrobacterium binary vectors for plant transformation. Plant Mol Biol 25: 989–994. 7919218

61. Clough SJ, Bent AF (1998) Floral dip: a simplified method for Agrobacterium-mediated transformation of Arabidopsis thaliana. Plant J 16: 735–743. 10069079

62. Eswar N, Webb B, Marti-Renom MA, Madhusudhan MS, Eramian D, et al. (2006) Comparative protein structure modeling using Modeller. Curr Protoc Bioinformatics Chapter 5: Unit 5 6. doi: 10.1002/0471250953.bi0907s13 18428773

63. Ramachandran GN, Ramakrishnan C, Sasisekharan V (1963) Stereochemistry of polypeptide chain configurations. J Mol Biol 7: 95–99. 13990617

64. Luthy R, Bowie JU, Eisenberg D (1992) Assessment of protein models with three-dimensional profiles. Nature 356: 83–85. 1538787

65. Ye Y, Godzik A (2003) Flexible structure alignment by chaining aligned fragment pairs allowing twists. Bioinformatics 19 Suppl 2: ii246–255. 14534198

66. Czechowski T, Stitt M, Altmann T, Udvardi MK, Scheible WR (2005) Genome-wide identification and testing of superior reference genes for transcript normalization in Arabidopsis. Plant Physiol 139: 5–17. 16166256

67. Larionov A, Krause A, Miller W (2005) A standard curve based method for relative real time PCR data processing. BMC Bioinformatics 6: 62. 15780134

68. Bolstad BM, Irizarry RA, Astrand M, Speed TP (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19: 185–193. 12538238

69. Edgar R, Domrachev M, Lash AE (2002) Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30: 207–210. 11752295

70. Ossowski S, Schwab R, Weigel D (2008) Gene silencing in plants using artificial microRNAs and other small RNAs. Plant J 53: 674–690. doi: 10.1111/j.1365-313X.2007.03328.x 18269576

71. Palanivelu P (2013) DNA Polymerases: An Insight into Their Active Sites and Catalytic Mechanism. Int J Biochem Res Rev 3: 42.