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. 2021 Nov 8;7(11):1461–1474. doi: 10.1038/s41477-021-01008-7

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© The Author(s) 2021

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Fig. 7 — The initiation of RdDM begins with Pol II expression of the unmethylated locus (step 1), followed by siRNA production from that transcript by any member of the DCL family (step 2). The siRNAs are incorporated into a member of the AGO4-clade of proteins (step 3) and this can only target RdDM to complementary regions of the genome that are expressed (step 4). Cis action refers to a region that generates siRNAs and targets its own methylation, while in trans action the siRNAs are acting on a separate locus. The AGO4 targeting of a Pol II expressed region of the genome results in Pol V recruitment (step 5) and the first round of RdDM (step 6). This final methylated product can then enter the methylation-dependent pathway of continual Pol V recruitment guided by SUVH2/SUVH9. See Discussion for details. Created with BioRender.com.