MET18 Connects the Cytosolic Iron-Sulfur Cluster Assembly Pathway to Active DNA Demethylation in

English version České info

DNA cytosine methylation is a major epigenetic mark that confers transcriptional regulation. Active removal of DNA methylation is important for plants and mammals during development and in responses to various stress conditions. In the model plant species Arabidopsis thaliana, active DNA demethylation depends on a family of 5-methylcytosine DNA glycosylases/demethylases including ROS1, DME, and others. While the epigenetic function of this demethylase family is well-known, little is known about how their enzymatic activities may be regulated. In this report, we carried out a forward genetic screen for anti-silencing factors and identified MET18, a conserved component of cytosolic iron-sulfur cluster assembly (CIA) pathway in eukaryotes, as being required for the ROS1-dependent active DNA demethylation. Dysfunction of MET18 causes DNA hyper-methylation at thousands of genomic loci where DNA methylation is pruned by ROS1. In addition, ROS1 physically interacts with MET18 and other CIA pathway components; while a conserved iron-sulfur-binding motif is indispensable for ROS1 enzyme activity. Our results suggested that MET18 affects DNA demethylation by influencing ROS1 enzymatic activity via direct interaction with the iron-sulfur-binding motif of ROS1, highlighting a direct connection between iron-sulfur cluster assembly and active DNA demethylation.

Vyšlo v časopise: MET18 Connects the Cytosolic Iron-Sulfur Cluster Assembly Pathway to Active DNA Demethylation in. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005559
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005559

Souhrn

Zdroje

1. Law JA, Jacobsen SE (2010) Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet 11 : 204–220. doi: 10.1038/nrg2719 20142834

2. Zhu JK (2009) Active DNA demethylation mediated by DNA glycosylases. Annu Rev Genet 43 : 143–166. doi: 10.1146/annurev-genet-102108-134205 19659441

3. Zilberman D (2008) The evolving functions of DNA methylation. Curr Opin Plant Biol 11 : 554–559. doi: 10.1016/j.pbi.2008.07.004 18774331

4. Le TN, Schumann U, Smith NA, Tiwari S, Au PC, et al. (2014) DNA demethylases target promoter transposable elements to positively regulate stress responsive genes in Arabidopsis. Genome Biol 15 : 458. doi: 10.1186/s13059-014-0458-3 25228471

5. Yu A, Lepere G, Jay F, Wang J, Bapaume L, et al. (2013) Dynamics and biological relevance of DNA demethylation in Arabidopsis antibacterial defense. Proc Natl Acad Sci U S A 110 : 2389–2394. doi: 10.1073/pnas.1211757110 23335630

6. Morales-Ruiz T, Ortega-Galisteo AP, Ponferrada-Marin MI, Martinez-Macias MI, Ariza RR, et al. (2006) DEMETER and REPRESSOR OF SILENCING 1 encode 5-methylcytosine DNA glycosylases. Proc Natl Acad Sci U S A 103 : 6853–6858. 16624880

7. Le TN, Schumann U, Smith NA, Tiwari S, Au P, et al. (2014) DNA demethylases target promoter transposable elements to positively regulate stress responsive genes in Arabidopsis. Genome Biol 15 : 458. doi: 10.1186/s13059-014-0458-3 25228471

8. Zemach A, Kim MY, Hsieh PH, Coleman-Derr D, Eshed-Williams L, et al. (2013) The Arabidopsis nucleosome remodeler DDM1 allows DNA methyltransferases to access H1-containing heterochromatin. Cell 153 : 193–205. doi: 10.1016/j.cell.2013.02.033 23540698

9. Zhang H, Zhu JK (2012) Active DNA demethylation in plants and animals. Cold Spring Harb Symp Quant Biol 77 : 161–173. doi: 10.1101/sqb.2012.77.014936 23197304

10. Gong Z, Morales-Ruiz T, Ariza RR, Roldan-Arjona T, David L, et al. (2002) ROS1, a repressor of transcriptional gene silencing in Arabidopsis, encodes a DNA glycosylase/lyase. Cell 111 : 803–814. 12526807

11. Qian W, Miki D, Zhang H, Liu Y, Zhang X, et al. (2012) A histone acetyltransferase regulates active DNA demethylation in Arabidopsis. Science 336 : 1445–1448. doi: 10.1126/science.1219416 22700931

12. Ortega-Galisteo AP, Morales-Ruiz T, Ariza RR, Roldan-Arjona T (2008) Arabidopsis DEMETER-LIKE proteins DML2 and DML3 are required for appropriate distribution of DNA methylation marks. Plant Mol Biol 67 : 671–681. doi: 10.1007/s11103-008-9346-0 18493721

13. Agius F, Kapoor A, Zhu JK (2006) Role of the Arabidopsis DNA glycosylase/lyase ROS1 in active DNA demethylation. Proc Natl Acad Sci U S A 103 : 11796–11801. 16864782

14. Gehring M, Huh JH, Hsieh TF, Penterman J, Choi Y, et al. (2006) DEMETER DNA glycosylase establishes MEDEA polycomb gene self-imprinting by allele-specific demethylation. Cell 124 : 495–506. 16469697

15. Martinez-Macias MI, Qian W, Miki D, Pontes O, Liu Y, et al. (2012) A DNA 3' phosphatase functions in active DNA demethylation in Arabidopsis. Mol Cell 45 : 357–370. doi: 10.1016/j.molcel.2011.11.034 22325353

16. Li Y, Cordoba-Canero D, Qian W, Zhu X, Tang K, et al. (2015) An AP Endonuclease Functions in Active DNA Dimethylation and Gene Imprinting in Arabidopsis. PLoS Genet 11: e1004905. doi: 10.1371/journal.pgen.1004905 25569774

17. Qian W, Miki D, Lei M, Zhu X, Zhang H, et al. (2014) Regulation of active DNA demethylation by an alpha-crystallin domain protein in Arabidopsis. Mol Cell 55 : 361–371. doi: 10.1016/j.molcel.2014.06.008 25002145

18. Lang Z, Lei M, Wang X, Tang K, Miki D, et al. (2015) The Methyl-CpG-Binding Protein MBD7 Facilitates Active DNA Demethylation to Limit DNA Hyper-Methylation and Transcriptional Gene Silencing. Mol Cell 57 : 971–983. doi: 10.1016/j.molcel.2015.01.009 25684209

19. Zheng X, Pontes O, Zhu J, Miki D, Zhang F, et al. (2008) ROS3 is an RNA-binding protein required for DNA demethylation in Arabidopsis. Nature 455 : 1259–1262. doi: 10.1038/nature07305 18815596

20. White MF, Dillingham MS (2012) Iron-sulphur clusters in nucleic acid processing enzymes. Curr Opin Struct Biol 22 : 94–100. doi: 10.1016/j.sbi.2011.11.004 22169085

21. Buzas DM, Nakamura M, Kinoshita T (2014) Epigenetic role for the conserved Fe-S cluster biogenesis protein AtDRE2 in Arabidopsis thaliana. Proc Natl Acad Sci U S A 111 : 13565–13570. doi: 10.1073/pnas.1404058111 25197096

22. Mok YG, Uzawa R, Lee J, Weiner GM, Eichman BF, et al. (2010) Domain structure of the DEMETER 5-methylcytosine DNA glycosylase. Proc Natl Acad Sci U S A 107 : 19225–19230. doi: 10.1073/pnas.1014348107 20974931

23. Couturier J, Touraine B, Briat JF, Gaymard F, Rouhier N (2013) The iron-sulfur cluster assembly machineries in plants: current knowledge and open questions. Front Plant Sci 4 : 259. doi: 10.3389/fpls.2013.00259 23898337

24. Netz DJ, Mascarenhas J, Stehling O, Pierik AJ, Lill R (2014) Maturation of cytosolic and nuclear iron-sulfur proteins. Trends Cell Biol 24 : 303–312. doi: 10.1016/j.tcb.2013.11.005 24314740

25. Roy A, Solodovnikova N, Nicholson T, Antholine W, Walden WE (2003) A novel eukaryotic factor for cytosolic Fe-S cluster assembly. EMBO J 22 : 4826–4835. 12970194

26. Hausmann A, Aguilar Netz DJ, Balk J, Pierik AJ, Muhlenhoff U, et al. (2005) The eukaryotic P loop NTPase Nbp35: an essential component of the cytosolic and nuclear iron-sulfur protein assembly machinery. Proc Natl Acad Sci U S A 102 : 3266–3271. 15728363

27. Luo D, Bernard DG, Balk J, Hai H, Cui X (2012) The DUF59 family gene AE7 acts in the cytosolic iron-sulfur cluster assembly pathway to maintain nuclear genome integrity in Arabidopsis. Plant Cell 24 : 4135–4148. doi: 10.1105/tpc.112.102608 23104832

28. Balk J, Pierik AJ, Netz DJ, Muhlenhoff U, Lill R (2004) The hydrogenase-like Nar1p is essential for maturation of cytosolic and nuclear iron-sulphur proteins. EMBO J 23 : 2105–2115. 15103330

29. Balk J, Aguilar Netz DJ, Tepper K, Pierik AJ, Lill R (2005) The essential WD40 protein Cia1 is involved in a late step of cytosolic and nuclear iron-sulfur protein assembly. Mol Cell Biol 25 : 10833–10841. 16314508

30. Gari K, Leon Ortiz AM, Borel V, Flynn H, Skehel JM, et al. (2012) MMS19 links cytoplasmic iron-sulfur cluster assembly to DNA metabolism. Science 337 : 243–245. doi: 10.1126/science.1219664 22678361

31. Stehling O, Vashisht AA, Mascarenhas J, Jonsson ZO, Sharma T, et al. (2012) MMS19 assembles iron-sulfur proteins required for DNA metabolism and genomic integrity. Science 337 : 195–199. doi: 10.1126/science.1219723 22678362

32. Lei M, Zhang H, Julian R, Tang K, Xie S, et al. (2015) Regulatory link between DNA methylation and active demethylation in Arabidopsis. Proc Natl Acad Sci U S A 112 : 3553–3557. doi: 10.1073/pnas.1502279112 25733903

33. Lei M, La H, Lu K, Wang P, Miki D, et al. (2014) Arabidopsis EDM2 promotes IBM1 distal polyadenylation and regulates genome DNA methylation patterns. Proc Natl Acad Sci U S A 111 : 527–532. doi: 10.1073/pnas.1320106110 24248388

34. Wang X, Duan CG, Tang K, Wang B, Zhang H, et al. (2013) RNA-binding protein regulates plant DNA methylation by controlling mRNA processing at the intronic heterochromatin-containing gene IBM1. Proc Natl Acad Sci U S A 110 : 15467–15472. doi: 10.1073/pnas.1315399110 24003136

35. 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

36. Penterman J, Zilberman D, Huh JH, Ballinger T, Henikoff S, et al. (2007) DNA demethylation in the Arabidopsis genome. Proc Natl Acad Sci U S A 104 : 6752–6757. 17409185

37. Ponferrada-Marin MI, Parrilla-Doblas JT, Roldan-Arjona T, Ariza RR (2011) A discontinuous DNA glycosylase domain in a family of enzymes that excise 5-methylcytosine. Nucleic Acids Res 39 : 1473–1484. doi: 10.1093/nar/gkq982 21036872

38. Yamamuro C, Miki D, Zheng Z, Ma J, Wang J, et al. (2014) Overproduction of stomatal lineage cells in Arabidopsis mutants defective in active DNA demethylation. Nat Commun 5 : 4062. doi: 10.1038/ncomms5062 24898766

39. Zhu J, Kapoor A, Sridhar VV, Agius F, Zhu JK (2007) The DNA glycosylase/lyase ROS1 functions in pruning DNA methylation patterns in Arabidopsis. Curr Biol 17 : 54–59. 17208187

40. Cunningham RP, Asahara H, Bank JF, Scholes CP, Salerno JC, et al. (1989) Endonuclease III is an iron-sulfur protein. Biochemistry 28 : 4450–4455. 2548577

41. Rouault TA (2012) Biogenesis of iron-sulfur clusters in mammalian cells: new insights and relevance to human disease. Dis Model Mech 5 : 155–164. doi: 10.1242/dmm.009019 22382365

42. Papatriantafyllou M (2012) DNA Metabolism: MMS19: CIA agent for DNA-linked affairs. Nat Rev Mol Cell Biol 13 : 538. doi: 10.1038/nrm3411 22828929

43. Chanet R, Heude M (2003) Characterization of mutations that are synthetic lethal with pol3-13, a mutated allele of DNA polymerase delta in Saccharomyces cerevisiae. Curr Genet 43 : 337–350. 12759774

44. Kuo CF, McRee DE, Fisher CL, O'Handley SF, Cunningham RP, et al. (1992) Atomic structure of the DNA repair [4Fe-4S] enzyme endonuclease III. Science 258 : 434–440. 1411536

45. Boal AK, Genereux JC, Sontz PA, Gralnick JA, Newman DK, et al. (2009) Redox signaling between DNA repair proteins for efficient lesion detection. Proc Natl Acad Sci U S A 106 : 15237–15242. doi: 10.1073/pnas.0908059106 19720997

46. Keating ST, El-Osta A (2015) Epigenetics and metabolism. Circ Res 116 : 715–736. doi: 10.1161/CIRCRESAHA.116.303936 25677519

47. Carrer A, Wellen KE (2014) Metabolism and epigenetics: a link cancer cells exploit. Curr Opin Biotechnol 34 : 23–29. doi: 10.1016/j.copbio.2014.11.012 25461508

48. Earley KW, Haag JR, Pontes O, Opper K, Juehne T, et al. (2006) Gateway-compatible vectors for plant functional genomics and proteomics. Plant J 45 : 616–629. 16441352

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

50. Duan C, Zhang H, Tang K, Zhu X, Qian W, et al. (2014) Specific but interdependent functions for Arabidopsis AGO4 and AGO6 in RNA-directed DNA methylation. EMBO J.

51. Ponferrada-Marin MI, Martinez-Macias MI, Morales-Ruiz T, Roldan-Arjona T, Ariza RR (2010) Methylation-independent DNA binding modulates specificity of Repressor of Silencing 1 (ROS1) and facilitates demethylation in long substrates. J Biol Chem 285 : 23032–23039. doi: 10.1074/jbc.M110.124578 20489198

52. Yoo SD, Cho YH, Sheen J (2007) Arabidopsis mesophyll protoplasts: a versatile cell system for transient gene expression analysis. Nat Protoc 2 : 1565–1572. 17585298

53. Law JA, Ausin I, Johnson LM, Vashisht AA, Zhu JK, et al. (2010) A protein complex required for polymerase V transcripts and RNA -⁠ directed DNA methylation in Arabidopsis. Curr Biol 20 : 951–956. doi: 10.1016/j.cub.2010.03.062 20409711

54. Wang P, Du Y, Hou Y, Zhao Y, Hsu C, et al. (2014) Nitric oxide negatively regulates abscisic acid signaling in guard cells by S-nitrosylation of OST1. Proc Natl Acad Sci U S A.