Non-canonical RNA-directed DNA methylation

A Corrigendum to this article was published on 12 December 2016

Abstract

Small RNA-directed DNA methylation (RdDM) has been extensively studied in plants, resulting in a deep understanding of a major ‘canonical RdDM’ mechanism. However, current models of canonical RdDM cannot explain how this self-perpetuating mechanism is initiated. Recent investigations into the initiation of epigenetic silencing have determined that there are several alternative ‘non-canonical RdDM’ pathways that function through distinct mechanisms to modify chromatin. This Review aims to illustrate the diversity of non-canonical RdDM mechanisms described to date, recognize common themes within this dizzying array of interconnected pathways, and identify the key unanswered questions remaining in this field.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: The canonical RdDM pathway.
Figure 2: PTGS in plants.
Figure 3: Pol II transcripts target DNA methylation through the non-canonical RdDM pathways.
Figure 4: Less understood mechanisms of non-canonical RdDM.

References

  1. 1

    Wassenegger, M., Heimes, S., Riedel, L. & Sänger, H. L. RNA-directed de novo methylation of genomic sequences in plants. Cell 76, 567–576 (1994).

    CAS  Article  Google Scholar 

  2. 2

    Volpe, T. A. et al. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297, 1833–1837 (2002).

    CAS  Article  Google Scholar 

  3. 3

    Hamilton, A., Voinnet, O., Chappell, L. & Baulcombe, D. Two classes of short interfering RNA in RNA silencing. EMBO J. 21, 4671–4679 (2002).

    CAS  Article  Google Scholar 

  4. 4

    Castel, S. E. & Martienssen, R. A. RNA interference in the nucleus: roles for small RNAs in transcription, epigenetics and beyond. Nat. Rev. Genet. 14, 100–112 (2013).

    CAS  Article  Google Scholar 

  5. 5

    Heard, E. & Martienssen, R. A. Transgenerational epigenetic inheritance: myths and mechanisms. Cell 157, 95–109 (2014).

    CAS  Article  Google Scholar 

  6. 6

    Hamilton, A. J. & Baulcombe, D. C. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286, 950–952 (1999).

    CAS  Article  Google Scholar 

  7. 7

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

    CAS  Article  Google Scholar 

  8. 8

    Law, J. A., Vashisht, A. A., Wohlschlegel, J. A. & Jacobsen, S. E. SHH1, a homeodomain protein required for DNA methylation, as well as RDR2, RDM4, and chromatin remodeling factors, associate with RNA polymerase IV. PLoS Genet. 7, e1002195 (2011).

    CAS  Article  Google Scholar 

  9. 9

    Haag, J. R. et al. In vitro transcription activities of Pol IV, Pol V, and RDR2 reveal coupling of Pol IV and RDR2 for dsRNA synthesis in plant RNA silencing. Mol. Cell 48, 811–818 (2012).

    CAS  Article  Google Scholar 

  10. 10

    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 

  11. 11

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

    CAS  Article  Google Scholar 

  12. 12

    Havecker, E. R. et al. The Arabidopsis RNA-directed DNA methylation Argonautes functionally diverge based on their expression and interaction with target loci. Plant Cell 22, 321–334 (2010).

    CAS  Article  Google Scholar 

  13. 13

    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).

    CAS  Article  Google Scholar 

  14. 14

    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).

    CAS  Article  Google Scholar 

  15. 15

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

    CAS  Article  Google Scholar 

  16. 16

    Herr, A. J., Jensen, M. B., Dalmay, T. & Baulcombe, D. C. RNA polymerase IV directs silencing of endogenous DNA. Science 308, 118–120 (2005).

    CAS  Article  Google Scholar 

  17. 17

    Liu, L. & Chen, X. RNA quality control as a key to suppressing RNA silencing of endogenous genes in plants. Mol. Plant 9, 826–836 (2016).

    CAS  Article  Google Scholar 

  18. 18

    Raja, P., Sanville, B. C., Buchmann, R. C. & Bisaro, D. M. Viral genome methylation as an epigenetic defense against geminiviruses. J. Virol. 82, 8997–9007 (2008).

    CAS  Article  Google Scholar 

  19. 19

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

    CAS  Article  Google Scholar 

  20. 20

    Panda, K. et al. Full-length autonomous transposable elements are preferentially targeted by expression-dependent forms of RNA-directed DNA methylation. Genome Biol. 17, 170 (2016).

    Article  Google Scholar 

  21. 21

    Henderson, I. R. et al. Dissecting Arabidopsis thaliana DICER function in small RNA processing, gene silencing and DNA methylation patterning. Nat. Genet. 38, 721–725 (2006).

    CAS  Article  Google Scholar 

  22. 22

    Wu, L. et al. DNA methylation mediated by a microRNA pathway. Mol. Cell 38, 465–475 (2010).

    CAS  Article  Google Scholar 

  23. 23

    Slotkin, R. K., Freeling, M. & Lisch, D. Heritable transposon silencing initiated by a naturally occurring transposon inverted duplication. Nat. Genet. 37, 641–644 (2005).

    CAS  Article  Google Scholar 

  24. 24

    Vazquez, F., Blevins, T., Ailhas, J., Boller, T. & Meins, F. Evolution of Arabidopsis MIR genes generates novel microRNA classes. Nucleic Acids Res. 36, 6429–6438 (2008).

    CAS  Article  Google Scholar 

  25. 25

    Chellappan, P. et al. siRNAs from miRNA sites mediate DNA methylation of target genes. Nucleic Acids Res. 38, 6883–6894 (2010).

    CAS  Article  Google Scholar 

  26. 26

    Khraiwesh, B. et al. Transcriptional control of gene expression by microRNAs. Cell 140, 111–122 (2010).

    CAS  Article  Google Scholar 

  27. 27

    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).

    CAS  Article  Google Scholar 

  28. 28

    Allen, E., Xie, Z., Gustafson, A. M. & Carrington, J. C. microRNA-directed phasing during trans-acting siRNA biogenesis in plants. Cell 121, 207–221 (2005).

    CAS  Article  Google Scholar 

  29. 29

    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).

    CAS  Article  Google Scholar 

  30. 30

    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).

    CAS  Article  Google Scholar 

  31. 31

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

    Article  Google Scholar 

  32. 32

    Gasciolli, V., Mallory, A. C., Bartel, D. P. & Vaucheret, H. Partially redundant functions of Arabidopsis DICER-like enzymes and a role for DCL4 in producing trans-acting siRNAs. Curr. Biol. 15, 1494–1500 (2005).

    CAS  Article  Google Scholar 

  33. 33

    Pontier, D. et al. NERD, a plant-specific GW protein, defines an additional RNAi-dependent chromatin-based pathway in Arabidopsis. Mol. Cell 48, 121–132 (2012).

    CAS  Article  Google Scholar 

  34. 34

    Garcia, D. et al. Ago hook and RNA helicase motifs underpin dual roles for SDE3 in antiviral defense and silencing of nonconserved intergenic regions. Mol. Cell 48, 109–120 (2012).

    CAS  Article  Google Scholar 

  35. 35

    Wei, W. et al. A role for small RNAs in DNA double-strand break repair. Cell 149, 101–112 (2012).

    CAS  Article  Google Scholar 

  36. 36

    Zhang, Z., Liu, X., Guo, X., Wang, X.-J. & Zhang, X. Arabidopsis AGO3 predominantly recruits 24-nt small RNAs to regulate epigenetic silencing. Nat. Plants 2, 16049 (2016).

    CAS  Article  Google Scholar 

  37. 37

    Ye, R. et al. A Dicer-independent route for biogenesis of siRNAs that direct DNA methylation in Arabidopsis. Mol. Cell 61, 222–235 (2016).

    CAS  Article  Google Scholar 

  38. 38

    Yang, D.-L. et al. Dicer-independent RNA-directed DNA methylation in Arabidopsis. Cell Res. 26, 66–82 (2016).

    CAS  Article  Google Scholar 

  39. 39

    Zemach, A. et al. The Arabidopsis nucleosome remodeler DDM1 allows DNA methyltransferases to access H1-containing heterochromatin. Cell 153, 193–205 (2013).

    CAS  Article  Google Scholar 

  40. 40

    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).

    CAS  Article  Google Scholar 

  41. 41

    Jackel, J. N., Storer, J. M., Coursey, T. & Bisaro, D. M. Arabidopsis RNA polymerases IV and V are required to establish H3K9 methylation, but not cytosine methylation, on geminivirus chromatin. J. Virol. 90, 7529–7540 (2016).

    CAS  Article  Google Scholar 

  42. 42

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

    CAS  Article  Google Scholar 

  43. 43

    Blevins, T. et al. A two-step process for epigenetic inheritance in Arabidopsis. Mol. Cell 54, 30–42 (2014).

    CAS  Article  Google Scholar 

  44. 44

    Johnson, L. M. et al. SRA- and SET-domain-containing proteins link RNA polymerase V occupancy to DNA methylation. Nature 507, 124–128 (2014).

    CAS  Article  Google Scholar 

  45. 45

    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  Google Scholar 

  46. 46

    Bond, D. M. & Baulcombe, D. C. Epigenetic transitions leading to heritable, RNA-mediated de novo silencing in Arabidopsis thaliana. Proc. Natl Acad. Sci. USA 112, 917–922 (2015).

    CAS  Article  Google Scholar 

  47. 47

    Fultz, D., Choudury, S. G. & Slotkin, R. K. Silencing of active transposable elements in plants. Curr. Opin. Plant Biol. 27, 67–76 (2015).

    CAS  Article  Google Scholar 

  48. 48

    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).

    CAS  Article  Google Scholar 

  49. 49

    Du, J., 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).

    CAS  Article  Google Scholar 

  50. 50

    Creasey, K. M. et al. miRNAs trigger widespread epigenetically activated siRNAs from transposons in Arabidopsis. Nature 508, 411–415 (2014).

    CAS  Article  Google Scholar 

  51. 51

    Bousios, A. et al. A role for palindromic structures in the cis-region of maize Sirevirus LTRs in transposable element evolution and host epigenetic response. Genome Res. 26, 226–237 (2016).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

D.C.-G. is supported by a Nuevo Leon state fellowship from the Mexico National Council of Science and Technology. The Slotkin lab is supported by U.S. National Science Foundation grants MCB-1252370 and MCB-1608392.

Author information

Affiliations

Authors

Corresponding author

Correspondence to R. Keith Slotkin.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Cuerda-Gil, D., Slotkin, R. Non-canonical RNA-directed DNA methylation. Nature Plants 2, 16163 (2016). https://doi.org/10.1038/nplants.2016.163

Download citation

Further reading

Search

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing