In this issue of Genes & Development , Wierzbicki and colleagues (pp. 1825–1836) examine the current model of RNA-directed DNA methylation (RdDM) by determining genome-wide distributions of RNA polymerase V (Pol V) occupancy, siRNAs, and DNA methylation. Their data support the key role of base-pairing between Pol V transcripts and siRNAs in targeting de novo DNA methylation. Importantly, the study also reveals unexpected complexity and provides a global view of the RdDM pathway.
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