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Non-canonical RNA-directed DNA methylation

Nature Plants volume 2, Article number: 16163 (2016) Cite this article

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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.

Identification of RNA-directed chromatin modification first occured in plants, where the accumulation of double-stranded RNA (dsRNA) resulted in sequence-specific targeting of cytosine DNA methylation1. Eight years later, small interfering RNAs (siRNAs) were identified as the causal molecule directing the deposition of DNA methylation and methylation of histone H3 at lysine 9 (H3K9me), resulting in the formation of stable heterochromatin2,3. Subsequently, siRNA-mediated heterochromatin formation (through methylation of cytosines or H3K9) was demonstrated in Caenorhabditis elegans, Drosophila and mice (reviewed in ref. 4), confirming that small RNAs are potent drivers of heterochromatic marks throughout the eukaryotic kingdoms. In plants, unlike animals, DNA methylation is not erased every generation, but rather epigenetically inherited (reviewed in ref. 5), explaining why transgenerational epigenetic inheritance patterns were first discovered and are more frequently observed in plants. This Review focuses on the different small RNA-guided pathways that establish heritable patterns of DNA methylation. Canonical and non-canonical forms of RdDM are compared and contrasted, with specific emphasis on the interconnection between post-transcriptional silencing and the establishment of chromatin marks.

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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.

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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.

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Authors and Affiliations

  1. Department of Molecular Genetics, The Ohio State University, 500 Aronoff Laboratory, 318 West Twelfth Avenue, Columbus, 43210, Ohio, USA

    Diego Cuerda-Gil & R. Keith Slotkin

  2. Center for RNA Biology, The Ohio State University, 105 Biological Sciences Building, 484 West Twelfth Avenue, Columbus, 43210, Ohio, USA

    R. Keith Slotkin

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Correspondence to R. Keith Slotkin.

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

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