RdDM

RdDM, or RNA-directed DNA methylation, is an epigenetic mechanism in plants that directs de novo cytosine methylation to transposable elements and other repetitive sequences using small RNAs, thereby contributing to transcriptional silencing and genome stability. The pathway is best characterized in flowering plants, such as Arabidopsis thaliana, and interacts with histone modification to reinforce silencing.

The process begins with RNA polymerase IV transcribing targeted genomic regions into single-stranded RNAs, which are converted into double-stranded RNA by RNA-dependent RNA polymerase RDR2. Dicer-like protein DCL3 processes these into 24-nucleotide small interfering RNAs (siRNAs). The siRNAs are loaded into Argonaute proteins, primarily AGO4 and AGO6, guiding them to complementary transcripts produced by RNA polymerase V. Pol V transcripts and associated chromatin recruit the DDR complex (DRD1, DMS3, RDM1), which acts to bridge the siRNA-AGO complex and the methyltransferase machinery. The de novo DNA methyltransferase DRM2 is recruited to establish methylation at cytosines in CG, CHG, and CHH contexts.

Maintenance and context-specific patterns of methylation follow establishment. CG methylation is maintained by MET1, CHG by CMT3, and CHH by CMT2 and, in many regions, RdDM itself. RdDM activity is linked with specific histone marks such as H3K9me2 and is modulated by factors including SHH1 and the CLSY family. The pathway plays a crucial role in silencing transposons, regulating gene expression, and contributing to epigenetic variation in development and stress responses.