#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Methylation-Sensitive Expression of a DNA Demethylase Gene Serves As an Epigenetic Rheostat


Organisms must adapt to dynamic and variable internal and external environments. Maintaining homeostasis in core biological processes is crucial to minimizing the deleterious consequences of environmental fluctuations. Genomes are also dynamic and variable, and must be robust against stresses, including the invasion of genomic parasites, such as transposable elements (TEs). In this work we present the discovery of an epigenetic rheostat in plants that maintains homeostasis in levels of DNA methylation. DNA methylation typically silences transcription of TEs. Because there is positive feedback between existing and de novo DNA methylation, it is critical that methylation is not allowed to spread and potentially silence transcription of genes. To maintain homeostasis, methylation promotes the production of a demethylase enzyme that removes methylation from gene-proximal regions. The demethylation of genes is therefore always maintained in concert with the levels of methylation suppressing TEs. In addition, this DNA demethylating enzyme also represses its own production in a negative feedback loop. Together, these feedback mechanisms shed new light on how the conflict between gene expression and genome defense is maintained in homeostasis. The presence of this rheostat in multiple species suggests it is an evolutionary conserved adaptation.


Vyšlo v časopise: Methylation-Sensitive Expression of a DNA Demethylase Gene Serves As an Epigenetic Rheostat. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005142
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005142

Souhrn

Organisms must adapt to dynamic and variable internal and external environments. Maintaining homeostasis in core biological processes is crucial to minimizing the deleterious consequences of environmental fluctuations. Genomes are also dynamic and variable, and must be robust against stresses, including the invasion of genomic parasites, such as transposable elements (TEs). In this work we present the discovery of an epigenetic rheostat in plants that maintains homeostasis in levels of DNA methylation. DNA methylation typically silences transcription of TEs. Because there is positive feedback between existing and de novo DNA methylation, it is critical that methylation is not allowed to spread and potentially silence transcription of genes. To maintain homeostasis, methylation promotes the production of a demethylase enzyme that removes methylation from gene-proximal regions. The demethylation of genes is therefore always maintained in concert with the levels of methylation suppressing TEs. In addition, this DNA demethylating enzyme also represses its own production in a negative feedback loop. Together, these feedback mechanisms shed new light on how the conflict between gene expression and genome defense is maintained in homeostasis. The presence of this rheostat in multiple species suggests it is an evolutionary conserved adaptation.


Zdroje

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

2. Dowen RH, Pelizzola M, Schmitz RJ, Lister R, Dowen JM, Nery JR, et al. Widespread dynamic DNA methylation in response to biotic stress. Proc Natl Acad Sci. 2012;109: E2183–E2191. doi: 10.1073/pnas.1209329109 22733782

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

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

5. Steward N, Ito M, Yamaguchi Y, Koizumi N, Sano H. Periodic DNA Methylation in Maize Nucleosomes and Demethylation by Environmental Stress. J Biol Chem. 2002;277: 37741–37746. 12124387

6. Ariel F, Jegu T, Latrasse D, Romero-Barrios N, Christ A, Benhamed M, et al. Noncoding Transcription by Alternative RNA Polymerases Dynamically Regulates an Auxin-Driven Chromatin Loop. Mol Cell. 2014;55: 383–396. doi: 10.1016/j.molcel.2014.06.011 25018019

7. Gehring M, Bubb KL, Henikoff S. Extensive Demethylation of Repetitive Elements During Seed Development Underlies Gene Imprinting. Science. 2009;324: 1447–1451. doi: 10.1126/science.1171609 19520961

8. Calarco JP, Borges F, Donoghue MTA, Van Ex F, Jullien PE, Lopes T, et al. Reprogramming of DNA Methylation in Pollen Guides Epigenetic Inheritance via Small RNA. Cell. 2012;151: 194–205. doi: 10.1016/j.cell.2012.09.001 23000270

9. Gent JI, Madzima TF, Bader R, Kent MR, Zhang X, Stam M, et al. Accessible DNA and Relative Depletion of H3K9me2 at Maize Loci Undergoing RNA-Directed DNA Methylation. Plant Cell Online. 2014; tpc.114.130427.

10. Zheng Q, Rowley MJ, Böhmdorfer G, Sandhu D, Gregory BD, Wierzbicki AT. RNA polymerase V targets transcriptional silencing components to promoters of protein-coding genes. Plant J. 2013;73: 179–189.

11. Pontier D, Picart C, Roudier F, Garcia D, Lahmy S, Azevedo J, et al. NERD, a Plant-Specific GW Protein, Defines an Additional RNAi-Dependent Chromatin-Based Pathway in Arabidopsis. Mol Cell. 2012;48: 121–132. doi: 10.1016/j.molcel.2012.07.027 22940247

12. McCue AD, Nuthikattu S, Reeder SH, Slotkin RK. Gene Expression and Stress Response Mediated by the Epigenetic Regulation of a Transposable Element Small RNA. PLoS Genet. 2012;8: e1002474. doi: 10.1371/journal.pgen.1002474 22346759

13. Johnson LM, Du J, Hale CJ, Bischof S, Feng S, Chodavarapu RK, et al. SRA- and SET-domain-containing proteins link RNA polymerase V occupancy to DNA methylation. Nature. 2014;507: 124–128. doi: 10.1038/nature12931 24463519

14. Zhong X, Du J, Hale CJ, Gallego-Bartolome J, Feng S, Vashisht AA, et al. Molecular Mechanism of Action of Plant DRM De Novo DNA Methyltransferases. Cell. 2014;157: 1050–1060. doi: 10.1016/j.cell.2014.03.056 24855943

15. Lindroth AM, Shultis D, Jasencakova Z, Fuchs J, Johnson L, Schubert D, et al. Dual histone H3 methylation marks at lysines 9 and 27 required for interaction with CHROMOMETHYLASE3. EMBO J. 2004;23: 4286–4296. 15457214

16. Zemach A, Kim MY, Hsieh P-H, Coleman-Derr D, Eshed-Williams L, Thao K, et al. The Arabidopsis Nucleosome Remodeler DDM1 Allows DNA Methyltransferases to Access H1-Containing Heterochromatin. Cell. 2013;153: 193–205. doi: 10.1016/j.cell.2013.02.033 23540698

17. Stroud H, Do T, Du J, Zhong X, Feng S, Johnson L, et al. Non-CG methylation patterns shape the epigenetic landscape in Arabidopsis. Nat Struct Mol Biol. 2014;21: 64–72. doi: 10.1038/nsmb.2735 24336224

18. Wang X, Weigel D, Smith LM. Transposon Variants and Their Effects on Gene Expression in Arabidopsis. PLoS Genet. 2013;9: e1003255. doi: 10.1371/journal.pgen.1003255 23408902

19. Penterman J, Zilberman D, Huh JH, Ballinger T, Henikoff S, Fischer RL. DNA demethylation in the Arabidopsis genome. Proc Natl Acad Sci. 2007;104: 6752–6757. 17409185

20. Lister R, O’Malley RC, Tonti-Filippini J, Gregory BD, Berry CC, Millar AH, et al. Highly Integrated Single-Base Resolution Maps of the Epigenome in Arabidopsis. Cell. 2008;133: 523–536. doi: 10.1016/j.cell.2008.03.029 18423832

21. Yamamuro C, Miki D, Zheng Z, Ma J, Wang J, Yang Z, et al. Overproduction of stomatal lineage cells in Arabidopsis mutants defective in active DNA demethylation. Nat Commun. 2014;5.

22. Zilberman D, Gehring M, Tran RK, Ballinger T, Henikoff S. Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription. Nat Genet. 2007;39: 61–69. 17128275

23. Huettel B, Kanno T, Daxinger L, Aufsatz W, Matzke AJM, Matzke M. Endogenous targets of RNA-directed DNA methylation and Pol IV in Arabidopsis. EMBO J. 2006;25: 2828–2836. 16724114

24. Mathieu O, Reinders J, Čaikovski M, Smathajitt C, Paszkowski J. Transgenerational Stability of the Arabidopsis Epigenome Is Coordinated by CG Methylation. Cell. 2007;130: 851–862. 17803908

25. Penterman J, Uzawa R, Fischer RL. Genetic Interactions between DNA Demethylation and Methylation in Arabidopsis. Plant Physiol. 2007;145: 1549–1557. 17951456

26. Rigal M, Kevei Z, Pélissier T, Mathieu O. DNA methylation in an intron of the IBM1 histone demethylase gene stabilizes chromatin modification patterns. EMBO J. 2012;31: 2981–2993. doi: 10.1038/emboj.2012.141 22580822

27. Bernatavichute YV, Zhang X, Cokus S, Pellegrini M, Jacobsen SE. Genome-Wide Association of Histone H3 Lysine Nine Methylation with CHG DNA Methylation in Arabidopsis thaliana. PLoS ONE. 2008;3: e3156. doi: 10.1371/journal.pone.0003156 18776934

28. Zhong X, Hale CJ, Law JA, Johnson LM, Feng S, Tu A, et al. DDR complex facilitates global association of RNA polymerase V to promoters and evolutionarily young transposons. Nat Struct Mol Biol. 2012;19: 870–875. doi: 10.1038/nsmb.2354 22864289

29. Rajagopalan R, Vaucheret H, Trejo J, Bartel DP. A diverse and evolutionarily fluid set of microRNAs in Arabidopsis thaliana. Genes Dev. 2006;20: 3407–3425. 17182867

30. Pignatta D, Erdmann RM, Scheer E, Picard CL, Bell GW, Gehring M. Natural epigenetic polymorphisms lead to intraspecific variation in Arabidopsis gene imprinting. eLife. 2014;3: e03198. doi: 10.7554/eLife.03198 24994762

31. Luff B, Pawlowski L, Bender J. An inverted repeat triggers cytosine methylation of identical sequences in Arabidopsis. Mol Cell. 1999;3: 505–511. 10230403

32. Gong Z, Morales-Ruiz T, Ariza RR, Roldán-Arjona T, David L, Zhu J-K. ROS1, a Repressor of Transcriptional Gene Silencing in Arabidopsis, Encodes a DNA Glycosylase/Lyase. Cell. 2002;111: 803–814. 12526807

33. Till BJ, Reynolds SH, Greene EA, Codomo CA, Enns LC, Johnson JE, et al. Large-Scale Discovery of Induced Point Mutations With High-Throughput TILLING. Genome Res. 2003;13: 524–530. 12618384

34. Fahlgren N, Jogdeo S, Kasschau KD, Sullivan CM, Chapman EJ, Laubinger S, et al. MicroRNA Gene Evolution in Arabidopsis lyrata and Arabidopsis thaliana. Plant Cell Online. 2010;22: 1074–1089. doi: 10.1105/tpc.110.073999 20407027

35. Jia Y, Lisch DR, Ohtsu K, Scanlon MJ, Nettleton D, Schnable PS. Loss of RNA–Dependent RNA Polymerase 2 (RDR2) Function Causes Widespread and Unexpected Changes in the Expression of Transposons, Genes, and 24-nt Small RNAs. PLoS Genet. 2009;5: e1000737. doi: 10.1371/journal.pgen.1000737 19936292

36. Madzima TF, Huang J, McGinnis KM. Chromatin structure and gene expression changes associated with loss of MOP1 activity in Zea mays. Epigenetics. 2014;9: 1047–1059. doi: 10.4161/epi.29022 24786611

37. Erhard KF, Talbot J-ERB, Deans NC, McClish AE, Hollick JB. Nascent Transcription Affected by RNA Polymerase IV in Zea mays. Genetics. 2015; genetics.115.174714.

38. Li Q, Eichten SR, Hermanson PJ, Zaunbrecher VM, Song J, Wendt J, et al. Genetic Perturbation of the Maize Methylome. Plant Cell Online. 2014;26: 4602–4616. doi: 10.1105/tpc.114.133140 25527708

39. Shibuya K, Fukushima S, Takatsuji H. RNA-directed DNA methylation induces transcriptional activation in plants. Proc Natl Acad Sci. 2009;106: 1660–1665. doi: 10.1073/pnas.0809294106 19164525

40. Becker C, Hagmann J, Müller J, Koenig D, Stegle O, Borgwardt K, et al. Spontaneous epigenetic variation in the Arabidopsis thaliana methylome. Nature. 2011;480: 245–249. doi: 10.1038/nature10555 22057020

41. Schmitz RJ, Schultz MD, Lewsey MG, O’Malley RC, Urich MA, Libiger O, et al. Transgenerational Epigenetic Instability Is a Source of Novel Methylation Variants. Science. 2011;334: 369–373. doi: 10.1126/science.1212959 21921155

42. Schoft VK, Chumak N, Choi Y, Hannon M, Garcia-Aguilar M, Machlicova A, et al. Function of the DEMETER DNA glycosylase in the Arabidopsis thaliana male gametophyte. Proc Natl Acad Sci. 2011;108: 8042–8047. doi: 10.1073/pnas.1105117108 21518889

43. Ibarra CA, Feng X, Schoft VK, Hsieh T-F, Uzawa R, Rodrigues JA, et al. Active DNA Demethylation in Plant Companion Cells Reinforces Transposon Methylation in Gametes. Science. 2012;337: 1360–1364. doi: 10.1126/science.1224839 22984074

44. Deleris A, Stroud H, Bernatavichute Y, Johnson E, Klein G, Schubert D, et al. Loss of the DNA Methyltransferase MET1 Induces H3K9 Hypermethylation at PcG Target Genes and Redistribution of H3K27 Trimethylation to Transposons in Arabidopsis thaliana. PLoS Genet. 2012;8: e1003062. doi: 10.1371/journal.pgen.1003062 23209430

45. Baylin SB, Jones PA. A decade of exploring the cancer epigenome—biological and translational implications. Nat Rev Cancer. 2011;11: 726–734. doi: 10.1038/nrc3130 21941284

46. Yang H, Liu Y, Bai F, Zhang J-Y, Ma S-H, Liu J, et al. Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation. Oncogene. 2013;32: 663–669. doi: 10.1038/onc.2012.67 22391558

47. Livak KJ, Schmittgen TD. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2-ddCt Method. Methods. 2001;25: 402–408. 11846609

48. Czechowski T, Stitt M, Altmann T, Udvardi MK, Scheible W-R. Genome-Wide Identification and Testing of Superior Reference Genes for Transcript Normalization in Arabidopsis. Plant Physiol. 2005;139: 5–17. 16166256

49. Lin Y, Zhang C, Lan H, Gao S, Liu H, Liu J, et al. Validation of Potential Reference Genes for qPCR in Maize across Abiotic Stresses, Hormone Treatments, and Tissue Types. PLoS ONE. 2014;9: e95445. doi: 10.1371/journal.pone.0095445 24810581

50. Xiao W, Gehring M, Choi Y, Margossian L, Pu H, Harada JJ, et al. Imprinting of the MEA Polycomb Gene Is Controlled by Antagonism between MET1 Methyltransferase and DME Glycosylase. Dev Cell. 2003;5: 891–901. 14667411

51. Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004;32: 1792–1797. 15034147

52. Hetzl J, Foerster AM, Raidl G, Scheid OM. CyMATE: a new tool for methylation analysis of plant genomic DNA after bisulphite sequencing. Plant J. 2007;51: 526–536. 17559516

53. Miki D, Shimamoto K. Simple RNAi Vectors for Stable and Transient Suppression of Gene Function in Rice. Plant Cell Physiol. 2004;45: 490–495. 15111724

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

55. Zemach A, Kim MY, Silva P, Rodrigues JA, Dotson B, Brooks MD, et al. Local DNA hypomethylation activates genes in rice endosperm. Proc Natl Acad Sci. 2010;107: 18729–18734. doi: 10.1073/pnas.1009695107 20937895

56. Larsson A. AliView: a fast and lightweight alignment viewer and editor for large datasets. Bioinformatics. 2014; btu531.

57. Ronquist F, Huelsenbeck JP. MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics. 2003;19: 1572–1574. 12912839

58. Posada D. jModelTest: Phylogenetic Model Averaging. Mol Biol Evol. 2008;25: 1253–1256. doi: 10.1093/molbev/msn083 18397919

59. Morton T, Petricka J, Corcoran DL, Li S, Winter CM, et al. Paired-End Analysis of Transcription Start Sites in Arabidopsis Reveals Plant-Specific Promoter Signatures. Plant Cell. 2014;26: 2746–2760. doi: 10.1105/tpc.114.125617 25035402

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2015 Číslo 3
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#