RNA-Directed DNA Methylation

This article may be too technical for most readers to understand. Please help improve this article to make it understandable to non-experts, without removing the technical details. The talk page may contain suggestions.  (May 2010)

RNA-directed DNA methylation (RdDM) is an epigenetic process first elucidated in plants whereby small double-stranded RNAs (dsRNA's) are processed to guide methylation to complementary DNA loci. In the model plant organism Arabidopsis thaliana, these small dsRNA's may be generated from three sources:

• Viral replication intermediates
• Products of the endogenous RNA-dependent RNA polymerase
• Transcribed inverted repeats

These dsRNAs are then processed to direct histone 3 lysine 9 (H3K9) methylation via Ago4 and the SUVH (Suppressor of Variegation Homolog) histone methyltransferase family. This H3K9 dimethylation is then putatively bound by the cytosine methyltransferase CMT3, which methylates cytosines in a non-CG context.

These marks, H3K9 dimethylation and cytosine methylation, are canonical marks of gene silencing. Thus small double stranded RNAs generated in diverse contexts bring about transcriptional silencing at specific loci.

References

• PNAS 2004 Review Article
• JCS 2004 Review Article
• Hypothesis of initiation of DNA methylation de novo and allelic exclusion by small RNAs