Seeing the forest for the trees: a wide perspective on RNA-directed DNA methylation

Abstract

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.

Figure 1.

A genome-wide view of Pol V functions and de novo DNA methylation in Arabidopsis. For the chromosome depicted in the center of the figure, black and yellow indicate the centromeric and pericentromeric regions, respectively. Red bars on the chromosome show regions of interest, as illustrated in A–F. (A,B) Some Pol V-occupied loci exhibit neither 24-nt siRNA production nor any cytosine methylation (A), while most overlap sites of both 24-nt siRNA production and cytosine methylation in the CHH context (^mCHH), which are indicative of RdDM (B). (C) Pol V also associates with DNA sequences that contain cytosine methylation other than ^mCHH, possibly contributing to RdDM-independent silencing . In the nrpd1, nrpe1, and nrpd/e2 mutants, positions of cytosine methylation in the CHH context can be lost, gained, or retained relative to the wild type (WT), as indicated. (D) Loss of ^mCHH can be attributed to dysfunction of the Pol IV- and Pol V-dependent RdDM pathway. (E) Gain or retention of ^mCHH in the mutants may be mediated through Pol II-dependent RdDM and/or DNA methylation that is recruited simply via protein interactions. See the text for additional information.