Dynamics and function of DNA methylation in plants

Abstract

DNA methylation is a conserved epigenetic modification that is important for gene regulation and genome stability. Aberrant patterns of DNA methylation can lead to plant developmental abnormalities. A specific DNA methylation state is an outcome of dynamic regulation by de novo methylation, maintenance of methylation and active demethylation, which are catalysed by various enzymes that are targeted by distinct regulatory pathways. In this Review, we discuss DNA methylation in plants, including methylating and demethylating enzymes and regulatory factors, and the coordination of methylation and demethylation activities by a so-called methylstat mechanism; the functions of DNA methylation in regulating transposon silencing, gene expression and chromosome interactions; the roles of DNA methylation in plant development; and the involvement of DNA methylation in plant responses to biotic and abiotic stress conditions.

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Fig. 1: RNA-directed DNA methylation pathways in Arabidopsis thaliana.
Fig. 2: Dynamic regulation of DNA methylation in plants.
Fig. 3: ROS1-mediated active DNA demethylation in Arabidopsis thaliana.
Fig. 4: Cellular functions of DNA methylation in plants.
Fig. 5: Roles of DNA methylation in plant growth and development.
Fig. 6: Stress-responsive changes in epigenetic modifications and possible stress memory.

References

  1. 1.

    Robertson, K. D. DNA methylation and human disease. Nat. Rev. Genet. 6, 597–610 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Slotkin, R. K. & Martienssen, R. Transposable elements and the epigenetic regulation of the genome. Nat. Rev. Genet. 8, 272–285 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Lang, Z. et al. Critical roles of DNA demethylation in the activation of ripening-induced genes and inhibition of ripening-repressed genes in tomato fruit. Proc. Natl Acad. Sci. USA 114, E4511–E4519 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Cortellino, S. et al. Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair. Cell 146, 67–79 (2011).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  5. 5.

    Zhu, J. K. Active DNA demethylation mediated by DNA glycosylases. Annu. Rev. Genet. 43, 143–166 (2009).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  6. 6.

    Wu, S. C. & Zhang, Y. Active DNA demethylation: many roads lead to Rome. Nat. Rev. Mol. Cell Biol. 11, 607–620 (2010).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  7. 7.

    Law, J. A. & Jacobsen, S. E. Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat. Rev. Genet. 11, 204–220 (2010).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  8. 8.

    Zhang, H. & Zhu, J. K. Active DNA demethylation in plants and animals. Cold Spring Harb. Symp. Quant. Biol. 77, 161–173 (2012).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  9. 9.

    He, X. J., Chen, T. & Zhu, J. K. Regulation and function of DNA methylation in plants and animals. Cell Res. 21, 442–465 (2011).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  10. 10.

    Watanabe, T. et al. Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science 332, 848–852 (2011).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  11. 11.

    Matzke, M. A. & Mosher, R. A. RNA-directed DNA methylation: an epigenetic pathway of increasing complexity. Nat. Rev. Genet. 15, 394–408 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Zhang, X. et al. Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis. Cell 126, 1189–1201 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Lister, R. et al. Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell 133, 523–536 (2008).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  14. 14.

    Henderson, I. R. & Jacobsen, S. E. Epigenetic inheritance in plants. Nature 447, 418–424 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Zhang, H. & Zhu, J. K. RNA-directed DNA methylation. Curr. Opin. Plant Biol. 14, 142–147 (2011).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  16. 16.

    Pikaard, C. S., Haag, J. R., Pontes, O. M., Blevins, T. & Cocklin, R. A transcription fork model for Pol IV and Pol V-dependent RNA-directed DNA methylation. Cold Spring Harb. Symp. Quant. Biol. 77, 205–212 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Zhong, X. et al. Molecular mechanism of action of plant DRM de novo DNA methyltransferases. Cell 157, 1050–1060 (2014).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  18. 18.

    Gao, Z. et al. An RNA polymerase II- and AGO4-associated protein acts in RNA-directed DNA methylation. Nature 465, 106–109 (2010).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  19. 19.

    He, X. J. et al. An effector of RNA-directed DNA methylation in Arabidopsis is an ARGONAUTE 4-and RNA-binding protein. Cell 137, 498–508 (2009).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  20. 20.

    Bies-Etheve, N. et al. RNA-directed DNA methylation requires an AGO4-interacting member of the SPT5 elongation factor family. EMBO Rep. 10, 649–654 (2009).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  21. 21.

    Zhang, H. et al. An Rrp6-like protein positively regulates noncoding RNA levels and DNA methylation in Arabidopsis. Mol. Cell 54, 418–430 (2014).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  22. 22.

    Ausin, I., Mockler, T. C., Chory, J. & Jacobsen, S. E. IDN1 and IDN2 are required for de novo DNA methylation in Arabidopsis thaliana. Nat. Struct. Mol. Biol. 16, 1325–1327 (2009).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  23. 23.

    Zheng, Z. et al. An SGS3-like protein functions in RNA-directed DNA methylation and transcriptional gene silencing in Arabidopsis. Plant J. 62, 92–99 (2010).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  24. 24.

    Ausin, I. et al. INVOLVED IN DE NOVO 2-containing complex involved in RNA-directed DNA methylation in Arabidopsis. Proc. Natl Acad. Sci. USA 109, 8374–8381 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Zhang, C. J. et al. IDN2 and its paralogs form a complex required for RNA-directed DNA methylation. PLoS Genet. 8, e1002693 (2012).

    Article  CAS  Google Scholar 

  26. 26.

    Finke, A., Kuhlmann, M. & Mette, M. F. IDN2 has a role downstream of siRNA formation in RNA-directed DNA methylation. Epigenetics 7, 950–960 (2012).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  27. 27.

    Xie, M., Ren, G. D., Zhang, C. & Yu, B. The DNA- and RNA-binding protein FACTOR of DNA METHYLATION 1 requires XH domain-mediated complex formation for its function in RNA-directed DNA methylation. Plant J. 72, 491–500 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Zhu, Y. Y., Rowley, M. J., Bohmdorfer, G. & Wierzbicki, A. T. A. SWI/SNF chromatin-remodeling complex acts in noncoding RNA-mediated transcriptional silencing. Mol. Cell 49, 298–309 (2013).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  29. 29.

    Law, J. A. et al. Polymerase IV occupancy at RNA-directed DNA methylation sites requires SHH1. Nature 498, 385–389 (2013).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  30. 30.

    Zhang, H. et al. DTF1 is a core component of RNA-directed DNA methylation and may assist in the recruitment of Pol IV. Proc. Natl Acad. Sci. USA 110, 8290–8295 (2013). References 29 and 30 reveal a key step in POL IV recruitment to a subset of RdDM target regions.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Smith, L. M. et al. An SNF2 protein associated with nuclear RNA silencing and the spread of a silencing signal between cells in Arabidopsis. Plant Cell 19, 1507–1521 (2007).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  32. 32.

    Kanno, T. et al. Involvement of putative SNF2 chromatin remodeling protein DRD1 in RNA-directed DNA methylation. Curr. Biol. 14, 801–805 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Kanno, T. et al. A structural-maintenance-of-chromosomes hinge domain-containing protein is required for RNA-directed DNA methylation. Nat. Genet. 40, 670–675 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Law, J. A. et al. A protein complex required for polymerase V transcripts and RNA- directed DNA methylation in Arabidopsis. Curr. Biol. 20, 951–956 (2010).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  35. 35.

    Zhong, X. H. et al. DDR complex facilitates global association of RNA polymerase V to promoters and evolutionarily young transposons. Nat. Struct. Mol. Biol. 19, 870–875 (2012).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  36. 36.

    Liu, Z. W. et al. The SET domain proteins SUVH2 and SUVH9 are required for Pol V occupancy at RNA-directed DNA methylation loci. PLoS Genet. 10, e1003948 (2014).

    Article  CAS  Google Scholar 

  37. 37.

    Johnson, L. M. et al. SRA- and SET-domain-containing proteins link RNA polymerase V occupancy to DNA methylation. Nature 507, 124–128 (2014). References 35 and 37 reveal how POL V may be recruited to some RdDM loci.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  38. 38.

    Wierzbicki, A. T., Haag, J. R. & Pikaard, C. S. Noncoding transcription by RNA polymerase Pol IVb/Pol V mediates transcriptional silencing of overlapping and adjacent genes. Cell 135, 635–648 (2008). This study identifies POL V-transcribed scaffold RNAs in the RdDM pathway.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  39. 39.

    Wierzbicki, A. T. et al. Spatial and functional relationships among Pol V-associated loci, Pol IV-dependent siRNAs, and cytosine methylation in the Arabidopsis epigenome. Genes Dev. 26, 1825–1836 (2012).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  40. 40.

    Blevins, T. et al. Identification of Pol IV and RDR2-dependent precursors of 24 nt siRNAs guiding de novo DNA methylation in Arabidopsis. eLife 4, e09591 (2015).

    Article  Google Scholar 

  41. 41.

    Li, S. F. et al. Detection of Pol IV/RDR2-dependent transcripts at the genomic scale in Arabidopsis reveals features and regulation of siRNA biogenesis. Genome Res. 25, 235–245 (2015).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  42. 42.

    Zhai, J. et al. A one precursor one siRNA model for Pol IV-dependent siRNA biogenesis. Cell 163, 445–455 (2015).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  43. 43.

    Yang, D. L. et al. Dicer-independent RNA-directed DNA methylation in Arabidopsis. Cell Res. 26, 1264 (2016). This DNA methylome analysis uncovers DCL-independent methylation at the majority of RdDM loci.

    PubMed Central  Article  PubMed  Google Scholar 

  44. 44.

    Ye, R. Q. et al. A Dicer-independent route for biogenesis of siRNAs that direct DNA methylation in Arabidopsis. Mol. Cell 61, 222–235 (2016). References 40–44 identify and characterize POL IV-transcribed ncRNAs.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Zheng, B. et al. Intergenic transcription by RNA polymerase II coordinates Pol IV and Pol V in siRNA-directed transcriptional gene silencing in Arabidopsis. Genes Dev. 23, 2850–2860 (2009). This study establishes an important role for POL II in regulating RdDM through the generation of siRNAs and scaffold RNAs.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  46. 46.

    Duan, C. G. et al. Specific but interdependent functions for Arabidopsis AGO4 and AGO6 in RNA-directed DNA methylation. EMBO J. 34, 581–592 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Wu, L., Mao, L. & Qi, Y. Roles of dicer-like and argonaute proteins in TAS-derived small interfering RNA-triggered DNA methylation. Plant Physiol. 160, 990–999 (2012).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  48. 48.

    Nuthikattu, S. et al. The initiation of epigenetic silencing of active transposable elements is triggered by RDR6 and 21–22 nucleotide small interfering RNAs. Plant Physiol. 162, 116–131 (2013). This study reveals RDR6-dependent non-canonical RdDM at transcriptionally active transposons.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  49. 49.

    McCue, A. D. et al. ARGONAUTE 6 bridges transposable element mRNA-derived siRNAs to the establishment of DNA methylation. EMBO J. 34, 20–35 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Mari-Ordonez, A. et al. Reconstructing de novo silencing of an active plant retrotransposon. Nat. Genet. 45, 1029–1039 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Lang, Z. & Gong, Z. Small RNA biogenesis: novel roles of an RNase III enzyme. Nat. Plants 2, 16021 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Ausin, I., Greenberg, M. V., Li, C. F. & Jacobsen, S. E. The splicing factor SR45 affects the RNA-directed DNA methylation pathway in Arabidopsis. Epigenetics 7, 29–33 (2012).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  53. 53.

    Huang, C. F. et al. A pre-mRNA-splicing factor is required for RNA-directed DNA methylation in Arabidopsis. PLoS Genet. 9, e1003779 (2013).

    Article  CAS  Google Scholar 

  54. 54.

    Dou, K. et al. The PRP6-like splicing factor STA1 is involved in RNA-directed DNA methylation by facilitating the production of Pol V-dependent scaffold RNAs. Nucleic Acids Res. 41, 8489–8502 (2013).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  55. 55.

    Zhang, C. J. et al. The splicing machinery promotes RNA-directed DNA methylation and transcriptional silencing in Arabidopsis. EMBO J. 32, 1128–1140 (2013).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  56. 56.

    Kankel, M. W. et al. Arabidopsis MET1 cytosine methyltransferase mutants. Genetics 163, 1109–1122 (2003).

    PubMed Central  CAS  PubMed  Google Scholar 

  57. 57.

    Song, J., Rechkoblit, O., Bestor, T. H. & Patel, D. J. Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation. Science 331, 1036–1040 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Du, J. M., Johnson, L. M., Jacobsen, S. E. & Patel, D. J. DNA methylation pathways and their crosstalk with histone methylation. Nat. Rev. Mol. Cell Biol. 16, 519–532 (2015).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  59. 59.

    Bostick, M. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science 317, 1760–1764 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Sharif, J. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature 450, 908–912 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Woo, H. R., Pontes, O., Pikaard, C. S. & Richards, E. J. VIM1, a methylcytosine-binding protein required for centromeric heterochromatinization. Genes Dev. 21, 267–277 (2007).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  62. 62.

    Woo, H. R., Dittmer, T. A. & Richards, E. J. Three SRA-domain methylcytosine-binding proteins cooperate to maintain global CpG methylation and epigenetic silencing in Arabidopsis. PLoS Genet. 4, e1000156 (2008).

    Article  CAS  Google Scholar 

  63. 63.

    Lindroth, A. M. et al. Requirement of CHROMOMETHYLASE3 for maintenance of CpXpG methylation. Science 292, 2077–2080 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Stroud, H. et al. Non-CG methylation patterns shape the epigenetic landscape in Arabidopsis. Nat. Struct. Mol. Biol. 21, 64–72 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Du, J. M. et al. Dual binding of chromomethylase domains to H3K9me2-containing nucleosomes directs DNA methylation in plants. Cell 151, 167–180 (2012).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  66. 66.

    Jackson, J. P., Lindroth, A. M., Cao, X. & Jacobsen, S. E. Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase. Nature 416, 556–560 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Malagnac, F., Bartee, L. & Bender, J. An Arabidopsis SET domain protein required for maintenance but not establishment of DNA methylation. EMBO J. 21, 6842–6852 (2002).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  68. 68.

    Jackson, J. P. et al. Dimethylation of histone H3 lysine 9 is a critical mark for DNA methylation and gene silencing in Arabidopsis thaliana. Chromosoma 112, 308–315 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. 69.

    Ebbs, M. L., Bartee, L. & Bender, J. H3 lysine 9 methylation is maintained on a transcribed inverted repeat by combined action of SUVH6 and SUVH4 methyltransferases. Mol. Cell. Biol. 25, 10507–10515 (2005).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  70. 70.

    Ebbs, M. L. & Bender, J. Locus-specific control of DNA methylation by the Arabidopsis SUVH5 histone methyltransferase. Plant Cell 18, 1166–1176 (2006).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  71. 71.

    Stroud, H., Greenberg, M. V. C., Feng, S. H., Bernatavichute, Y. V. & Jacobsen, S. E. Comprehensive analysis of silencing mutants reveals complex regulation of the Arabidopsis methylome. Cell 152, 352–364 (2013).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  72. 72.

    Du, J. M. et al. Mechanism of DNA methylation-directed histone methylation by KRYPTONITE. Mol. Cell 55, 495–504 (2014). References 65 and 72 provide the structural basis of the reinforcing loop between histone H3K9 methylation and the maintenance of DNA CHG methylation.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  73. 73.

    Huettel, B. et al. Endogenous targets of RNA-directed DNA methylation and Pol IV in Arabidopsis. EMBO J. 25, 2828–2836 (2006).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  74. 74.

    Zemach, A. et al. The Arabidopsis nucleosome remodeler DDM1 allows DNA methyltransferases to access H1-containing heterochromatin. Cell 153, 193–205 (2013). This study reveals the coordinated function of CMT2 and DDM1 in establishing RdDM-independent CHH methylation at the body region of long transposable elements.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  75. 75.

    Jeddeloh, J. A., Stokes, T. L. & Richards, E. J. Maintenance of genomic methylation requires a SWI2/SNF2-like protein. Nat. Genet. 22, 94–97 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. 76.

    Rocha, P. S. et al. The Arabidopsis HOMOLOGY-DEPENDENT GENE SILENCING1 gene codes for an S-adenosyl-L-homocysteine hydrolase required for DNA methylation-dependent gene silencing. Plant Cell 17, 404–417 (2005).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  77. 77.

    Zhang, H. et al. Sulfamethazine suppresses epigenetic silencing in Arabidopsis by impairing folate synthesis. Plant Cell 24, 1230–1241 (2012).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  78. 78.

    Zhou, H. R. et al. Folate polyglutamylation is involved in chromatin silencing by maintaining global DNA methylation and histone H3K9 dimethylation in Arabidopsis. Plant Cell 25, 2545–2559 (2013).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  79. 79.

    Groth, M. et al. MTHFD1 controls DNA methylation in Arabidopsis. Nat. Commun. 7, 11640 (2016).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  80. 80.

    Gong, Z. et al. ROS1, a repressor of transcriptional gene silencing in Arabidopsis, encodes a DNA glycosylase/lyase. Cell 111, 803–814 (2002). This study provides a genetic evidence for base excision repair-mediated active DNA demethylation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. 81.

    Gehring, M. et al. DEMETER DNA glycosylase establishes MEDEA polycomb gene self-imprinting by allele-specific demethylation. Cell 124, 495–506 (2006).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  82. 82.

    Ortega-Galisteo, A. P., Morales-Ruiz, T., Ariza, R. R. & Roldan-Arjona, T. Arabidopsis DEMETER-LIKE proteins DML2 and DML3 are required for appropriate distribution of DNA methylation marks. Plant Mol. Biol. 67, 671–681 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. 83.

    Wu, X. & Zhang, Y. TET-mediated active DNA demethylation: mechanism, function and beyond. Nat. Rev. Genet. 18, 517–534 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. 84.

    Agius, F., Kapoor, A. & Zhu, J. K. Role of the Arabidopsis DNA glycosylase/lyase ROS1 in active DNA demethylation. Proc. Natl Acad. Sci. USA 103, 11796–11801 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Morales-Ruiz, T. et al. DEMETER and REPRESSOR OF SILENCING 1 encode 5-methylcytosine DNA glycosylases. Proc. Natl Acad. Sci. USA 103, 6853–6858 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. 86.

    Penterman, J. et al. DNA demethylation in the Arabidopsis genome. Proc. Natl Acad. Sci. USA 104, 6752–6757 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. 87.

    Zhu, J. H., Kapoor, A., Sridhar, V. V., Agius, F. & Zhu, J. K. The DNA glycosylase/lyase ROS1 functions in pruning DNA methylation patterns in Arabidopsis. Curr. Biol. 17, 54–59 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. 88.

    Huh, J. H., Bauer, M. J., Hsieh, T. F. & Fischer, R. L. Cellular programming of plant gene imprinting. Cell 132, 735–744 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. 89.

    Martinez-Macias, M. I. et al. A DNA 3 ‘ phosphatase functions in active DNA demethylation in Arabidopsis. Mol. Cell 45, 357–370 (2012).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  90. 90.

    Lee, J. et al. AP endonucleases process 5-methylcytosine excision intermediates during active DNA demethylation in Arabidopsis. Nucleic Acids Res. 42, 11408–11418 (2014).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  91. 91.

    Li, Y. et al. An AP endonuclease functions in active DNA demethylation and gene imprinting in Arabidopsis. PLoS Genet. 11, e1004905 (2015).

    Article  CAS  Google Scholar 

  92. 92.

    Andreuzza, S. et al. DNA LIGASE I exerts a maternal effect on seed development in Arabidopsis thaliana. Development 137, 73–81 (2010).

    Article  CAS  PubMed  Google Scholar 

  93. 93.

    Li, Y., Duan, C. G., Zhu, X., Qian, W. & Zhu, J. K. A. DNA ligase required for active DNA demethylation and genomic imprinting in Arabidopsis. Cell Res. 25, 757–760 (2015).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  94. 94.

    Ponferrada-Marin, M. I., Roldan-Arjona, T. & Ariza, R. R. Demethylation initiated by ROS1 glycosylase involves random sliding along DNA. Nucleic Acids Res. 40, 11554–11562 (2012).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  95. 95.

    Gehring, M., Bubb, K. L. & Henikoff, S. Extensive demethylation of repetitive elements during seed development underlies gene imprinting. Science 324, 1447–1451 (2009).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  96. 96.

    Hsieh, T. F. et al. Genome-wide demethylation of Arabidopsis endosperm. Science 324, 1451–1454 (2009). References 95 and 96 uncover extensive demethylation at transposons in the Arabidopsis thaliana endosperm.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  97. 97.

    Ibarra, C. A. et al. Active DNA demethylation in plant companion cells reinforces transposon methylation in gametes. Science 337, 1360–1364 (2012).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  98. 98.

    Tang, K., Lang, Z., Zhang, H. & Zhu, J. K. The DNA demethylase ROS1 targets genomic regions with distinct chromatin modifications. Nat. Plants 2, 16169 (2016). This analysis reveals the chromatin features of regions targeted by the DNA demethylase ROS1 and identifies thousands of previously unknown RdDM targets.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  99. 99.

    Zheng, X. W. et al. ROS3 is an RNA-binding protein required for DNA demethylation in Arabidopsis. Nature 455, 1259–U1270 (2008).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  100. 100.

    Qian, W. et al. A histone acetyltransferase regulates active DNA demethylation in Arabidopsis. Science 336, 1445–1448 (2012). This study uncovers a chromatin regulator of ROS1-mediated active DNA demethylation.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  101. 101.

    Qian, W. et al. Regulation of active DNA demethylation by an alpha-crystallin domain protein in Arabidopsis. Mol. Cell 55, 361–371 (2014).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  102. 102.

    Lang, Z. et al. The methyl-CpG-binding protein MBD7 facilitates active DNA demethylation to limit DNA hyper-methylation and transcriptional gene silencing. Mol. Cell 57, 971–983 (2015).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  103. 103.

    Duan, C. G. et al. A pair of transposon-derived proteins function in a histone acetyltransferase complex for active DNA demethylation. Cell Res. 27, 226–240 (2017). References 102 and 103 identify the IDM protein complex, which regulates active DNA demethylation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. 104.

    Wang, C. Methyl-CpG-binding domain protein MBD7 is required for active DNA demethylation in Arabidopsis. Plant Physiol. 167, 905–914 (2015).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  105. 105.

    Li, X. J. et al. Antisilencing role of the RNA-directed DNA methylation pathway and a histone acetyltransferase in Arabidopsis. Proc. Natl Acad. Sci. USA 109, 11425–11430 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  106. 106.

    Lei, M. G. et al. Regulatory link between DNA methylation and active demethylation in Arabidopsis. Proc. Natl Acad. Sci. USA 112, 3553–3557 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. 107.

    Williams, B. P., Pignatta, D., Henikoff, S. & Gehring, M. Methylation-sensitive expression of a DNA demethylase gene serves as an epigenetic rheostat. PLOS Genet. 11, e1005142 (2015). References 106 and 107 identify a methylation-sensing genetic element that helps monitor DNA methylation status and achieve a dynamic balance between DNA methylation and demethylation.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  108. 108.

    Mathieu, O., Reinders, J., Caikovski, M., Smathajitt, C. & Paszkowski, J. Transgenerational stability of the Arabidopsis epigenome is coordinated by CG methylation. Cell 130, 851–862 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. 109.

    Williams, B. P. & Gehring, M. Stable transgenerational epigenetic inheritance requires a DNA methylation-sensing circuit. Nat. Commun. 8, 2124 (2017).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  110. 110.

    Hu, L. et al. Mutation of a major CG methylase in rice causes genome-wide hypomethylation, dysregulated genome expression, and seedling lethality. Proc. Natl Acad. Sci. USA 111, 10642–10647 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. 111.

    Erhard, K. F. et al. Nascent transcription affected by RNA polymerase IV in Zea mays. Genetics 199, 1107–1125 (2015).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  112. 112.

    Jones, M. J., Goodman, S. J. & Kobor, M. S. DNA methylation and healthy human aging. Aging Cell. 14, 924–932 (2015).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  113. 113.

    Baylin, S. B. & Jones, P. A. Epigenetic determinants of cancer. Cold Spring Harb. Perspect. Biol. 8, a019505 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. 114.

    Domcke, S. et al. Competition between DNA methylation and transcription factors determines binding of NRF1. Nature 528, 575–579 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. 115.

    Zhu, H., Wang, G. H. & Qian, J. Transcription factors as readers and effectors of DNA methylation. Nat. Rev. Genet. 17, 551–565 (2016).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  116. 116.

    Alleman, M. et al. An RNA-dependent RNA polymerase is required for paramutation in maize. Nature 442, 295–298 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. 117.

    Erhard, K. F. et al. RNA polymerase IV functions in paramutation in Zea mays. Science 323, 1201–1205 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. 118.

    Wei, L. Y. et al. Dicer-like 3 produces transposable element-associated 24-nt siRNAs that control agricultural traits in rice. Proc. Natl Acad. Sci. USA 111, 3877–3882 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. 119.

    Liu, R. et al. A DEMETER-like DNA demethylase governs tomato fruit ripening. Proc. Natl Acad. Sci. USA 112, 10804–10809 (2015). References 3 and 119 demonstrate the importance of active DNA demethylation for tomato fruit ripening.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. 120.

    Cokus, S. J. et al. Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature 452, 215–219 (2008).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  121. 121.

    Takuno, S. & Gaut, B. S. Gene body methylation is conserved between plant orthologs and is of evolutionary consequence. Proc. Natl Acad. Sci. USA 110, 1797–1802 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  122. 122.

    Niederhuth, C. E. et al. Widespread natural variation of DNA methylation within angiosperms. Genome Biol. 17, 194 (2016).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  123. 123.

    Bewick, A. J. et al. On the origin and evolutionary consequences of gene body DNA methylation. Proc. Natl Acad. Sci. USA 113, 9111–9116 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. 124.

    Bewick, A. J. et al. The evolution of CHROMOMETHYLASES and gene body DNA methylation in plants. Genome Biol. 18, 65 (2017).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  125. 125.

    Wollmann, H. et al. The histone H3 variant H3.3 regulates gene body DNA methylation in Arabidopsis thaliana. Genome Biol. 18, 94 (2017).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  126. 126.

    Kawakatsu, T. et al. Epigenomic diversity in a global collection of Arabidopsis thaliana accessions. Cell 166, 492–505 (2016). This study presents an epigenome analysis of the 1001 Genomes collection of Arabidopsis thaliana and provides an important resources for understanding how variation in DNA methylation correlates with phenotypes in natural A. thaliana populations.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  127. 127.

    Zilberman, D., Coleman-Derr, D., Ballinger, T. & Henikoff, S. Histone H2A. Z and DNA methylation are mutually antagonistic chromatin marks. Nature 456, 125–129 (2008).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  128. 128.

    Takuno, S. & Gaut, B. S. Body-methylated genes in Arabidopsis thaliana are functionally important and evolve slowly. Mol. Biol. Evol. 29, 219–227 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. 129.

    Neri, F. et al. Intragenic DNA methylation prevents spurious transcription initiation. Nature 543, 72–77 (2017).

    Article  CAS  Google Scholar 

  130. 130.

    Wang, X. et al. DNA methylation affects gene alternative splicing in plants: an example from rice. Mol. Plant 9, 305–307 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. 131.

    Ong-Abdullah, M. et al. Loss of Karma transposon methylation underlies the mantled somaclonal variant of oil palm. Nature 525, 533–537 (2015).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  132. 132.

    Wang, X. G. et al. RNA-binding protein regulates plant DNA methylation by controlling mRNA processing at the intronic heterochromatin-containing gene IBM1. Proc. Natl Acad. Sci. USA 110, 15467–15472 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  133. 133.

    Saze, H. et al. Mechanism for full-length RNA processing of Arabidopsis genes containing intragenic heterochromatin. Nat. Commun. 4, 2301 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. 134.

    Lei, M. G. et al. Arabidopsis EDM2 promotes IBM1 distal polyadenylation and regulates genome DNA methylation patterns. Proc. Natl Acad. Sci. USA 111, 527–532 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. 135.

    Duan, C. G. et al. A protein complex regulates RNA processing of intronic heterochromatin-containing genes in Arabidopsis. Proc. Natl Acad. Sci. USA 114, E7377–E7384 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. 136.

    Saze, H. Mechanism for full-length RNA processing of Arabidopsis genes containing intragenic heterochromatin. Nat. Commun. 4, 2301 (2013). References 132–136 identify the protein complex ASI1–AIPP1–EDM2, which controls RNA distal polyadenylation at genes with intronic heterochromatin.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. 137.

    Li, Q. et al. RNA-directed DNA methylation enforces boundaries between heterochromatin and euchromatin in the maize genome. Proc. Natl Acad. Sci. USA 112, 14728–14733 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. 138.

    Zakrzewski, F., Schmidt, M., Van Lijsebettens, M. & Schmidt, T. DNA methylation of retrotransposons, DNA transposons and genes in sugar beet (Beta vulgaris L.). Plant J. 90, 1156–1175 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. 139.

    Gouil, Q. & Baulcombe, D. C. DNA methylation signatures of the plant chromomethyltransferases. PLoS Genet. 12, e1006526 (2016).

    Article  CAS  Google Scholar 

  140. 140.

    Kato, M., Miura, A., Bender, J., Jacobsen, S. E. & Kakutani, T. Role of CG and non-CG methylation in immobilization of transposons in Arabidopsis. Curr. Biol. 13, 421–426 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. 141.

    Mirouze, M. et al. Selective epigenetic control of retrotransposition in Arabidopsis. Nature 461, 427–430 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. 142.

    Tsukahara, S. et al. Bursts of retrotransposition reproduced in Arabidopsis. Nature 461, 423–426 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. 143.

    Ito, H. et al. An siRNA pathway prevents transgenerational retrotransposition in plants subjected to stress. Nature 472, 115–119 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. 144.

    La, H. et al. A 5-methylcytosine DNA glycosylase/lyase demethylates the retrotransposon Tos17 and promotes its transposition in rice. Proc. Natl Acad. Sci. USA 108, 15498–15503 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  145. 145.

    Grob, S., Schmid, M. W. & Grossniklaus, U. Hi-C analysis in Arabidopsis identifies the KNOT, a structure with similarities to the flamenco Locus of Drosophila. Mol. Cell 55, 678–693 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. 146.

    Feng, S. et al. Genome-wide Hi-C analyses in wild-type and mutants reveal high-resolution chromatin interactions in Arabidopsis. Mol. Cell 55, 694–707 (2014). References 145 and 146 profile A. thaliana chromosome interactions and their correlation with various epigenetic modifications.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  147. 147.

    Rowley, M. J., Rothi, M. H., Bohmdorfer, G., Kucinski, J. & Wierzbicki, A. T. Long-range control of gene expression via RNA-directed DNA methylation. PLoS Genet. 13, e1006749 (2017).

    Article  CAS  Google Scholar 

  148. 148.

    Zemach, A. et al. Local DNA hypomethylation activates genes in rice endosperm. Proc. Natl Acad. Sci. USA 107, 18729–18734 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  149. 149.

    Park, K. et al. DNA demethylation is initiated in the central cells of Arabidopsis and rice. Proc. Natl Acad. Sci. USA 113, 15138–15143 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. 150.

    Slotkin, R. K. et al. Epigenetic reprogramming and small RNA silencing of transposable elements in pollen. Cell 136, 461–472 (2009). This study reveals intercellular silencing of sperm cell transposons by siRNAs that originated from the vegetative cell.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  151. 151.

    Martínez, G., Panda, K., Köhler, C. & Slotkin, R. K. Silencing in sperm cells is directed by RNA movement from the surrounding nurse cell. Nat. Plants. 2, 16030 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. 152.

    Ingouff, M. Live-cell analysis of DNA methylation during sexual reproduction in Arabidopsis reveals context and sex-specific dynamics controlled by noncanonical RdDM. Genes Dev. 31, 72–83 (2017).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  153. 153.

    Kawakatsu, T., Nery, J. R., Castanon, R. & Ecker, J. R. Dynamic DNA methylation reconfiguration during seed development and germination. Genome Biol. 18, 171 (2017).

    PubMed Central  Article  PubMed  Google Scholar 

  154. 154.

    Bouyer, D. DNA methylation dynamics during early plant life. Genome Biol. 18, 179 (2017).

    PubMed Central  Article  PubMed  Google Scholar 

  155. 155.

    Narsai, R. Extensive transcriptomic and epigenomic remodelling occurs during Arabidopsis thaliana germination. Genome Biol. 18, 172 (2017).

    PubMed Central  Article  PubMed  Google Scholar 

  156. 156.

    Lin, J. Y. Similarity between soybean and Arabidopsis seed methylomes and loss of non-CG methylation does not affect seed development. Proc. Natl Acad. Sci. USA 114, E9730–E9739 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. 157.

    Walker, J. Sexual-lineage-specific DNA methylation regulates meiosis in Arabidopsis. Nat. Genet. 50, 130–137 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. 158.

    Zhang, M. et al. Genome-wide high resolution parental-specific DNA and histone methylation maps uncover patterns of imprinting regulation in maize. Genome Res. 24, 167–176 (2014).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  159. 159.

    Klosinska, M., Picard, C. L. & Gehring, M. Conserved imprinting associated with unique epigenetic signatures in the Arabidopsis genus. Nat. Plants 2, 16145 (2016).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  160. 160.

    Rodrigues, J. A. et al. Imprinted expression of genes and small RNA is associated with localized hypomethylation of the maternal genome in rice endosperm. Proc. Natl Acad. Sci. USA 110, 7934–7939 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  161. 161.

    Pignatta, D. et al. Natural epigenetic polymorphisms lead to intraspecific variation in Arabidopsis gene imprinting. eLife 3, e03198 (2014).

    Article  Google Scholar 

  162. 162.

    Jullien, P. E., Katz, A., Oliva, M., Ohad, N. & Berger, F. Polycomb group complexes self-regulate imprinting of the Polycomb group gene MEDEA in Arabidopsis. Curr. Biol. 16, 486–492 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. 163.

    Hsieh, T. F. et al. Regulation of imprinted gene expression in Arabidopsis endosperm. Proc. Natl Acad. Sci. USA 108, 1755–1762 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  164. 164.

    Kinoshita, T. et al. One-way control of FWA imprinting in Arabidopsis endosperm by DNA methylation. Science 303, 521–523 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. 165.

    Bratzel, F. et al. Regulation of the new Arabidopsis imprinted gene AtBMI1C requires the interplay of different epigenetic mechanisms. Mol. Plant 5, 260–269 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. 166.

    Vu, T. M. et al. RNA-directed DNA methylation regulates parental genomic imprinting at several loci in Arabidopsis. Development 140, 2953–2960 (2013).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  167. 167.

    Moreno-Romero, J., Jiang, H., Santos-Gonzalez, J. & Kohler, C. Parental epigenetic asymmetry of PRC2-mediated histone modifications in the Arabidopsis endosperm. EMBO J. 35, 1298–1311 (2016).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  168. 168.

    Dong, X. M. et al. Dynamic and antagonistic allele-Specific epigenetic modifications controlling the expression of imprinted genes in maize endosperm. Mol. Plant 10, 442–455 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. 169.

    Baubec, T., Finke, A., Scheid, O. M. & Pecinka, A. Meristem-specific expression of epigenetic regulators safeguards transposon silencing in Arabidopsis. EMBO Rep. 15, 446–452 (2014).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  170. 170.

    Kawakatsu, T. et al. Unique cell-type-specific patterns of DNA methylation in the root meristem. Nat. Plants 2, 16058 (2016). This study demonstrates diversified epigenomes in different somatic cell types in A. thaliana roots.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  171. 171.

    Moritoh, S. et al. Targeted disruption of an orthologue of DOMAINS REARRANGED METHYLASE 2, OsDRM2, impairs the growth of rice plants by abnormal DNA methylation. Plant J. 71, 85–98 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. 172.

    Zhou, S. L. et al. Cooperation between the H3K27me3 chromatin mark and non-CG methylation in epigenetic regulation. Plant Physiol. 172, 1131–1141 (2016).

    PubMed Central  CAS  PubMed  Google Scholar 

  173. 173.

    Candaele, J. et al. Differential methylation during maize leaf growth targets developmentally regulated genes. Plant Physiol. 164, 1350–1364 (2014).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  174. 174.

    Yamamuro, C. et al. Overproduction of stomatal lineage cells in Arabidopsis mutants defective in active DNA demethylation. Nat. Commun. 5, 4062 (2014).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  175. 175.

    Wang, Y. H., Xue, X. Y., Zhu, J. K. & Dong, J. Demethylation of ERECTA receptor genes by IBM1 histone demethylase affects stomatal development. Development 143, 4452–4461 (2016). References 174 and 175 demonstrate the functional importance of ROS1-mediated active DNA methylation in plant development.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  176. 176.

    Zhong, S. et al. Single-base resolution methylomes of tomato fruit development reveal epigenome modifications associated with ripening. Nat. Biotechnol. 31, 154–159 (2013).

    Article  CAS  PubMed  Google Scholar 

  177. 177.

    Telias, A. et al. Apple skin patterning is associated with differential expression of MYB10. BMC Plant Biol. 11, 93 (2011).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  178. 178.

    El-Sharkawy, I., Liang, D. & Xu, K. N. Transcriptome analysis of an apple (Malus x domestica) yellow fruit somatic mutation identifies a gene network module highly associated with anthocyanin and epigenetic regulation. J. Exp. Bot. 66, 7359–7376 (2015).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  179. 179.

    Daccord, N. et al. High-quality de novo assembly of the apple genome and methylome dynamics of early fruit development. Nat. Genet. 49, 1099–1106 (2017).

    Article  CAS  PubMed  Google Scholar 

  180. 180.

    Manning, K. et al. A naturally occurring epigenetic mutation in a gene encoding an SBP-box transcription factor inhibits tomato fruit ripening. Nat. Genet. 38, 948–952 (2006).

    Article  CAS  PubMed  Google Scholar 

  181. 181.

    Zhang, X., Sun, J., Cao, X. & Song, X. Epigenetic mutation of RAV6 affects leaf angle and seed size in rice. Plant Physiol. 169, 2118–2128 (2015).

    PubMed Central  CAS  PubMed  Google Scholar 

  182. 182.

    Song, Q., Zhang, T., Stelly, D. M. & Chen, Z. J. Epigenomic and functional analyses reveal roles of epialleles in the loss of photoperiod sensitivity during domestication of allotetraploid cottons. Genome Biol. 18, 99 (2017).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  183. 183.

    Hofmeister, B. T., Lee, K., Rohr, N. A., Hall, D. W. & Schmitz, R. J. Stable inheritance of DNA methylation allows creation of epigenotype maps and the study of epiallele inheritance patterns in the absence of genetic variation. Genome Biol. 18, 155 (2017).

    PubMed Central  Article  PubMed  Google Scholar 

  184. 184.

    Reinders, J. et al. Compromised stability of DNA methylation and transposon immobilization in mosaic Arabidopsis epigenomes. Genes Dev. 23, 939–950 (2009).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  185. 185.

    Teixeira, F. K. et al. A role for RNAi in the selective correction of DNA methylation defects. Science 323, 1600–1604 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. 186.

    Catoni, M. et al. DNA sequence properties that predict susceptibility to epiallelic switching. EMBO J. 36, 617–628 (2017).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  187. 187.

    Johannes, F. et al. Assessing the impact of transgenerational epigenetic variation on complex traits. PLoS Genet. 5, e1000530 (2009).

    Article  CAS  Google Scholar 

  188. 188.

    Blevins, T., Wang, J., Pflieger, D., Pontvianne, F. & Pikaard, C. S. Hybrid incompatibility caused by an epiallele. Proc. Natl Acad. Sci. USA 114, 3702–3707 (2017).

    Article  CAS  PubMed  Google Scholar 

  189. 189.

    Chen, W. W. et al. Requirement of CHROMOMETHYLASE3 for somatic inheritance of the spontaneous tomato epimutation Colourless non-ripening. Sci. Rep. 5, 9192 (2015).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  190. 190.

    Dapp, M. Heterosis and inbreeding depression of epigenetic Arabidopsis hybrids. Nat. Plants. 1, 15092 (2015).

    Article  CAS  PubMed  Google Scholar 

  191. 191.

    Lauss, K. Parental DNA methylation states are associated with heterosis in epigenetic hybrids. Plant Physiol. 172, 1627–1645 (2017).

    Google Scholar 

  192. 192.

    Schmitz, R. J. Patterns of population epigenomic diversity. Nature 495, 193–198 (2013).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  193. 193.

    Dubin, M. J. DNA methylation in Arabidopsis has a genetic basis and shows evidence of local adaptation. eLife 4, e05255 (2015).

    Article  Google Scholar 

  194. 194.

    Satge, C. et al. Reprogramming of DNA methylation is critical for nodule development in Medicago truncatula. Nat. Plants 2, 16166 (2016).

    Article  CAS  PubMed  Google Scholar 

  195. 195.

    Nagymihaly, M. et al. Ploidy-dependent changes in the epigenome of symbiotic cells correlate with specific patterns of gene expression. Proc. Natl Acad. Sci. USA 114, 4543–4548 (2017).

    Article  CAS  PubMed  Google Scholar 

  196. 196.

    Rambani, A. et al. The methylome of soybean roots during the compatible interaction with the soybean Cyst nematode. Plant Physiol. 168, 1364–1377 (2015).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  197. 197.

    Hewezi, T. et al. Cyst nematode parasitism induces dynamic changes in the root epigenome. Plant Physiol. 174, 405–420 (2017).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  198. 198.

    Dowen, R. H. et al. Widespread dynamic DNA methylation in response to biotic stress. Proc. Natl Acad. Sci. USA 109, E2183–E2191 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  199. 199.

    Martinez, G., Castellano, M., Tortosa, M., Pallas, V. & Gomez, G. A pathogenic non-coding RNA induces changes in dynamic DNA methylation of ribosomal RNA genes in host plants. Nucleic Acids Res. 42, 1553–1562 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. 200.

    Castellano, M. et al. Changes in the DNA methylation pattern of the host male gametophyte of viroid-infected cucumber plants. J. Exp. Bot. 67, 5857–5868 (2016).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  201. 201.

    Agorio, A. & Vera, P. ARGONAUTE4 is required for resistance to Pseudomonas syringae in Arabidopsis. Plant Cell 19, 3778–3790 (2007).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  202. 202.

    Lopez, A., Ramirez, V., Garcia-Andrade, J., Flors, V. & Vera, P. The RNA silencing enzyme RNA polymerase V Is required for plant immunity. PLoS Genet. 7, e1002434 (2011).

    Article  CAS  Google Scholar 

  203. 203.

    Yu, A. et al. Dynamics and biological relevance of DNA demethylation in Arabidopsis antibacterial defense. Proc. Natl Acad. Sci. USA 110, 2389–2394 (2013). This study demonstrates an important role for active DNA demethylation in A. thaliana immune responses.

    Article  PubMed  PubMed Central  Google Scholar 

  204. 204.

    Le, T. N. et al. DNA demethylases target promoter transposable elements to positively regulate stress responsive genes in Arabidopsis. Genome Biol. 15, 458 (2014).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  205. 205.

    Sanchez, A. L., Stassen, J. H. M., Furci, L., Smith, L. M. & Ton, J. The role of DNA (de)methylation in immune responsiveness of Arabidopsis. Plant J. 88, 361–374 (2016).

    Article  CAS  Google Scholar 

  206. 206.

    Deng, Y. et al. Epigenetic regulation of antagonistic receptors confers rice blast resistance with yield balance. Science 355, 962–965 (2017).

    Article  CAS  Google Scholar 

  207. 207.

    Secco, D. et al. Stress induced gene expression drives transient DNA methylation changes at adjacent repetitive elements. eLife 4, e09343 (2015).

    Article  Google Scholar 

  208. 208.

    Eichten, S. R. & Springer, N. M. Minimal evidence for consistent changes in maize DNA methylation patterns following environmental stress. Front. Plant Sci. 6, 308 (2015).

    PubMed Central  Article  PubMed  Google Scholar 

  209. 209.

    Jiang, C. et al. Environmentally responsive genome-wide accumulation of de novo Arabidopsis thaliana mutations and epimutations. Genome Res. 24, 1821–1829 (2014).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  210. 210.

    Yong-Villalobos, L. et al. Methylome analysis reveals an important role for epigenetic changes in the regulation of the Arabidopsis response to phosphate starvation. Proc. Natl Acad. Sci. USA 112, E7293–E7302 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. 211.

    Khan, A. R. et al. Vernalization treatment induces site-specific DNA hypermethylation at the VERNALIZATION-A1 (VRN-A1) locus in hexaploid winter wheat. Bmc Plant Biol. 13, 209 (2013).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  212. 212.

    Xu, R. et al. Salt-induced transcription factor MYB74 is regulated by the RNA-directed DNA methylation pathway in Arabidopsis. J. Exp. Bot. 66, 5997–6008 (2015).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  213. 213.

    Liu, T. K., Li, Y., Duan, W. K., Huang, F. Y. & Hou, X. L. Cold acclimation alters DNA methylation patterns and confers tolerance to heat and increases growth rate in Brassica rapa. J. Exp. Bot. 68, 1213–1224 (2017).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  214. 214.

    Zheng, X. G. et al. Transgenerational epimutations induced by multi-generation drought imposition mediate rice plant’s adaptation to drought condition. Sci. Rep. 7, 39843 (2017).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  215. 215.

    Li, J. et al. Global DNA methylation variations after short-term heat shock treatment in cultured microspores of Brassica napus cv. Topas. Sci. Rep. 6, 38401 (2016).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  216. 216.

    Li, S. Y. et al. Laser irradiation-induced DNA methylation changes are heritable and accompanied with transpositional activation of mPing in Rice. Front. Plant Sci. 8, 363 (2017).

    PubMed Central  PubMed  Google Scholar 

  217. 217.

    Narsai, R. et al. Dynamic and rapid changes in the transcriptome and epigenome during germination and in developing rice (Oryza sativa) coleoptiles under anoxia and re-oxygenation. Plant J. 89, 805–824 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  218. 218.

    Lu, Y. C. et al. Genome-wide identification of DNA methylation provides insights into the association of gene expression in rice exposed to pesticide atrazine. Sci. Rep. 6, 18985 (2016).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  219. 219.

    Wibowo, A. et al. Hyperosmotic stress memory in Arabidopsis is mediated by distinct epigenetically labile sites in the genome and is restricted in the male germline by DNA glycosylase activity. eLife 5, e13546 (2016).

    Article  Google Scholar 

  220. 220.

    Chwialkowska, K., Nowakowska, U., Mroziewicz, A., Szarejko, I. & Kwasniewski, M. Water-deficiency conditions differently modulate the methylome of roots and leaves in barley (Hordeum vulgare L.). J. Exp. Bot. 67, 1109–1121 (2016).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  221. 221.

    Seta, A. et al. Post-translational regulation of the dicing activities of Arabidopsis DICER-LIKE 3 and 4 by inorganic phosphate and the redox state. Plant Cell Physiol. 58, 485–495 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  222. 222.

    Gugger, P. F., Fitz-Gibbon, S., Pellegrini, M. & Sork, V. L. Species-wide patterns of DNA methylation variation in Quercus lobata and their association with climate gradients. Mol. Ecol. 25, 1665–1680 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. 223.

    Liang, D. et al. Single-base-resolution methylomes of populus trichocarpa reveal the association between DNA methylation and drought stress. BMC Genet. 15 (Suppl. 1), S9 (2014).

    PubMed Central  Article  PubMed  Google Scholar 

  224. 224.

    Sanchez, D. H. & Paszkowski, J. Heat-induced release of epigenetic silencing reveals the concealed role of an imprinted plant gene. PLoS Genet. 10, e1004806 (2014).

    Article  CAS  Google Scholar 

  225. 225.

    Bocchini, M. et al. Iron deficiency in barley plants: phytosiderophore release, iron translocation, and DNA methylation. Front. Plant Sci. 6, 514 (2015).

    PubMed Central  Article  PubMed  Google Scholar 

  226. 226.

    Lang-Mladek, C. et al. Transgenerational inheritance and resetting of stress-induced loss of epigenetic gene silencing in Arabidopsis. Mol. Plant 3, 594–602 (2010).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  227. 227.

    Ganguly, D. R., Crisp, P. A., Eichten, S. R. & Pogson, B. J. The Arabidopsis DNA methylome is stable under transgenerational drought stress. Plant Physiol. 175, 1893–1912 (2017).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  228. 228.

    Zhang, B. et al. Chilling-induced tomato flavor loss is associated with altered volatile synthesis and transient changes in DNA methylation. Proc. Natl Acad. Sci. USA 113, 15580–12585 (2016).

    Google Scholar 

  229. 229.

    Amedeo, P., Habu, Y., Afsar, K., Mittelsten Scheid, O. & Paszkowski, J. Disruption of the plant gene MOM releases transcriptional silencing of methylated genes. Nature 405, 203–206 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. 230.

    Vaillant, I., Schubert, I., Tourmente, S. & Mathieu, O. MOM1 mediates DNA-methylation-independent silencing of repetitive sequences in Arabidopsis. EMBO Rep. 7, 1273–1278 (2006).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  231. 231.

    Numa, H. et al. Transduction of RNA-directed DNA methylation signals to repressive histone marks in Arabidopsis thaliana. EMBO J. 29, 352–362 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. 232.

    Iwasaki, M. & Paszkowski, J. Identification of genes preventing transgenerational transmission of stress-induced epigenetic states. Proc. Natl Acad. Sci. USA 111, 8547–8552 (2014). This study uncovers the fact that DDM1 and MOM1 redundantly control the erasure of stress-induced epigenetic memory during plant recovery from heat stress.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  233. 233.

    Saze, H. & Kakutani, T. Heritable epigenetic mutation of a transposon-flanked Arabidopsis gene due to lack of the chromatin-remodeling factor DDM1. EMBO J. 26, 3641–3652 (2007).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  234. 234.

    Zhang, Q. et al. Methylation interactions in Arabidopsis hybrids require RNA-directed DNA methylation and are influenced by genetic variation. Proc. Natl Acad. Sci. USA 113, E4248–E4256 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. 235.

    Stelpflug, S. C., Eichten, S. R., Hermanson, P. J., Springer, N. M. & Kaeppler, S. M. Consistent and heritable alterations of DNA methylation are induced by tissue culture in maize. Genetics 198, 209–218 (2014).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  236. 236.

    Stroud, H. et al. Plants regenerated from tissue culture contain stable epigenome changes in rice. eLife 2, e00354 (2013).

    Article  Google Scholar 

  237. 237.

    Hirochika, H., Sugimoto, K., Otsuki, Y., Tsugawa, H. & Kanda, M. Retrotransposons of rice involved in mutations induced by tissue culture. Proc. Natl Acad. Sci. USA 93, 7783–7788 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  238. 238.

    Vining, K. et al. Methylome reorganization during in vitro dedifferentiation and regeneration of Populus trichocarpa. BMC Plant Biol. 13, 92 (2013).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  239. 239.

    Schoof, H. et al. The stem cell population of Arabidopsis shoot meristems in maintained by a regulatory loop between the CLAVATA and WUSCHEL genes. Cell 100, 635–644 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  240. 240.

    Gordon, S. P. et al. Pattern formation during de novo assembly of the Arabidopsis shoot meristem. Development 134, 3539–3548 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  241. 241.

    Li, W. et al. DNA methylation and histone modifications regulate de novo shoot regeneration in Arabidopsis by modulating WUSCHEL expression and auxin signaling. PLoS Genet. 7, e1002243 (2011).

    Article  CAS  Google Scholar 

  242. 242.

    Shemer, O., Landau, U., Candela, H., Zemach, A. & Williams, L. E. Competency for shoot regeneration from Arabidopsis root explants is regulated by DNA methylation. Plant Sci. 238, 251–261 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors apologize to those colleagues whose work is not cited owing to space constraints. The work of the authors has been supported by the Chinese Academy of Sciences.

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Nature Reviews Molecular Cell Biology thanks F. Berger, V. Colot and X. Zhong for their contribution to the peer review of this work.

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H.Z. and J.-K.Z. researched data for the article, provided substantial contributions to the discussion of content and wrote the article. H.Z., Z.L. and J.-K.Z. reviewed and edited the manuscript before submission.

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Correspondence to Huiming Zhang or Jian-Kang Zhu.

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Glossary

AGO hook

A protein motif containing Gly–Trp or Try–Gly repeats, which mediate protein interactions with ARGONAUTE (AGO) proteins.

Ribosomal RNA-processing 6

(RRP6). A conserved single-stranded RNA nuclease with both negative and positive functions in RNA accumulation.

Trans-acting siRNA genes

Genes that encode transcripts that are cleaved by microRNAs, synthesized into double-stranded RNA and then cleaved again to produce trans-acting small interfering RNAs (siRNAs).

α-Crystallin domain

A motif of approximately 100 amino acids that is characteristic of evolutionarily conserved small heat shock proteins.

Helitron

A major class of eukaryotic transposons that transpose through rolling-circle replication.

Homeotic gene

A gene that controls pattern formation during development.

Mantled

A type of abnormality in oil palm male floral organs in which they transform into supernumerary carpels.

Columella cells

A layer of cells that form the root cap and protect the growing root tip.

Allotetraploid

A polyploid with four sets of chromosomes derived from two or more diverged taxa.

Heterosis

The increase in characteristics, such as size and yield, of a hybrid organism over those of its parents.

Nucleotide-binding and oligomerization domain-like receptors

Receptors that mediate recognition of pathogen avirulence effectors and activate immune responses.

Biotrophic pathogen

A pathogen that feeds on only live host cells.

Necrotrophic pathogens

Pathogens that feed on nutrients released from dead cells.

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Zhang, H., Lang, Z. & Zhu, JK. Dynamics and function of DNA methylation in plants. Nat Rev Mol Cell Biol 19, 489–506 (2018). https://doi.org/10.1038/s41580-018-0016-z

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