{"doi":"10.1038/s41477-021-01008-7","title":"An siRNA-guided ARGONAUTE protein directs RNA polymerase V to initiate DNA methylation","abstract":"In mammals and plants, cytosine DNA methylation is essential for the epigenetic repression of transposable elements and foreign DNA. In plants, DNA methylation is guided by small interfering RNAs (siRNAs) in a self-reinforcing cycle termed RNA-directed DNA methylation (RdDM). RdDM requires the specialized RNA polymerase V (Pol V), and the key unanswered question is how Pol V is first recruited to new target sites without pre-existing DNA methylation. We find that Pol V follows and is dependent on the recruitment of an AGO4-clade ARGONAUTE protein, and any siRNA can guide the ARGONAUTE protein to the new target locus independent of pre-existing DNA methylation. These findings reject long-standing models of RdDM initiation and instead demonstrate that siRNA-guided ARGONAUTE targeting is necessary, sufficient and first to target Pol V recruitment and trigger the cycle of RdDM at a transcribed target locus, thereby establishing epigenetic silencing.","journal":"Nature Plants","year":2021,"id":151486,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":83,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":644131,"name":"Kaushik Panda","orcid":"0000-0002-8217-472X","position":1,"is_corresponding":false},{"id":644132,"name":"Rachel Kirchner","orcid":"0000-0001-9925-8009","position":2,"is_corresponding":false},{"id":645241,"name":"Lauren McLain","orcid":null,"position":3,"is_corresponding":false},{"id":644133,"name":"Hayden Payne","orcid":"0009-0000-1719-4161","position":4,"is_corresponding":false},{"id":644134,"name":"John Reddy Peasari","orcid":"0000-0003-4140-0855","position":5,"is_corresponding":false},{"id":379237,"name":"Aman Y. Husbands","orcid":"0000-0003-4580-1779","position":6,"is_corresponding":false},{"id":77573,"name":"R. Keith Slotkin","orcid":"0000-0001-9582-3533","position":7,"is_corresponding":false},{"id":644135,"name":"Andrea D. McCue","orcid":"0000-0002-9634-6641","position":8,"is_corresponding":false},{"id":644130,"name":"Meredith J. Sigman","orcid":"0000-0001-5847-0206","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T23:43:16.823357Z","pmid":"34750500","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}