RNA-directed DNA methylation: an epigenetic pathway of increasing complexity

• Published in: Nature reviews. Genetics Vol. 15; no. 6; pp. 394 - 408
• Main Authors: Matzke, Marjori A., Mosher, Rebecca A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2014; Nature Publishing Group
• Subjects: 631/208/176/1988; 631/208/726/2001/1428; 631/337/384/521; 631/449/1659; Agriculture; Animal Genetics and Genomics; Biomedicine; Cancer Research; Cytoplasm; DNA methylation; DNA Methylation - physiology; DNA-Directed RNA Polymerases - genetics; DNA-Directed RNA Polymerases - metabolism; Enzymes; Epigenesis, Genetic - physiology; Epigenetic inheritance; Epigenetics; Eukaryota - physiology; Gene Function; Genetic transcription; Genomes; Human Genetics; Methylation; Proteins; review-article; RNA polymerase; RNA, Small Untranslated - genetics; RNA, Small Untranslated - metabolism; Yeast
• ISSN: 1471-0056; 1471-0064
• DOI: 10.1038/nrg3683

Key Points RNA-directed DNA methylation (RdDM) is prevalent in flowering plants and induces transcriptional silencing at repetitive DNA, including all types of transposons. During RdDM, RNA polymerase IV (Pol IV) initiates production of 24-nucleotide small interfering RNAs (siRNAs) that direct transcriptionally repressive DNA methylation to homologous Pol V-transcribed loci. Pol IV and Pol V are recruited to genomic regions that contain transcriptionally repressive epigenetic marks, thereby reinforcing and maintaining the silent state. Recent research has uncovered variations on the canonical RdDM pathway, including the involvement of RNA-DEPENDENT RNA POLYMERASE 6 (RDR6) and NEEDED FOR RDR2-INDEPENDENT DNA METHYLATION (NERD), which might allow 'young' (that is, recently acquired) transposons to come under the control of RdDM. In additional to transposon control, RdDM might help hosts to respond to biotic or abiotic challenges, or to faithfully transmit DNA methylation patterns to their offspring. RdDM might also affect germ cell specification and parent-specific gene expression. There is increasing evidence that siRNAs are used to communicate epigenetic states between homologous sequences within a nucleus or indeed between nuclei. RNA-directed DNA methylation (RdDM) is a major mechanism of transcriptional gene silencing in plants that is mediated through small interfering RNAs (siRNAs) and plant-specific RNA polymerases. This Review summarizes our latest understanding of RdDM, including its genomic targets, molecular mechanisms (such as emerging non-canonical pathways) and diverse biological roles. RNA-directed DNA methylation (RdDM) is the major small RNA-mediated epigenetic pathway in plants. RdDM requires a specialized transcriptional machinery that comprises two plant-specific RNA polymerases — Pol IV and Pol V — and a growing number of accessory proteins, the functions of which in the RdDM mechanism are only partially understood. Recent work has revealed variations in the canonical RdDM pathway and identified factors that recruit Pol IV and Pol V to specific target sequences. RdDM, which transcriptionally represses a subset of transposons and genes, is implicated in pathogen defence, stress responses and reproduction, as well as in interallelic and intercellular communication.