{"doi":"10.1038/s41594-021-00712-4","title":"SETDB1-like MET-2 promotes transcriptional silencing and development independently of its H3K9me-associated catalytic activity","abstract":"Transcriptionally silenced heterochromatin bearing methylation of histone H3 on lysine 9 (H3K9me) is critical for maintaining organismal viability and tissue integrity. Here we show that in addition to ensuring H3K9me, MET-2, the Caenorhabditis elegans homolog of the SETDB1 histone methyltransferase, has a noncatalytic function that contributes to gene repression. Subnuclear foci of MET-2 coincide with H3K9me deposition, yet these foci also form when MET-2 is catalytically deficient and H3K9me is compromised. Whereas met-2 deletion triggers a loss of silencing and increased histone acetylation, foci of catalytically deficient MET-2 maintain silencing of a subset of genes, blocking acetylation on H3K9 and H3K27. In normal development, this noncatalytic MET-2 activity helps to maintain fertility. Under heat stress MET-2 foci disperse, coinciding with increased acetylation and transcriptional derepression. Our study suggests that the noncatalytic, focus-forming function of this SETDB1-like protein and its intrinsically disordered cofactor LIN-61 is physiologically relevant.","journal":"Nature Structural & Molecular Biology","year":2022,"id":248754,"datarank":0.515098080672772,"base_score":3.4339872044851463,"endowment":3.4339872044851463,"self_citation_contribution":0.515098080672772,"citation_network_contribution":0.0,"self_endowment_contribution":0.515098080672772,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":551822,"name":"Stephen P. Methot","orcid":"0000-0003-2854-2226","position":1,"is_corresponding":false},{"id":340804,"name":"Véronique Kalck","orcid":null,"position":2,"is_corresponding":false},{"id":867821,"name":"Jan Seebacher","orcid":"0000-0002-7858-2720","position":3,"is_corresponding":false},{"id":81034,"name":"Daniel Heß","orcid":"0000-0002-1642-5404","position":4,"is_corresponding":false},{"id":65530,"name":"Susan M. Gasser","orcid":"0000-0003-3610-9123","position":5,"is_corresponding":false},{"id":339438,"name":"Jan Padeken","orcid":"0000-0001-6538-0946","position":6,"is_corresponding":false},{"id":551824,"name":"Colin Delaney","orcid":"0000-0001-6880-6973","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:24:14.794521Z","pmid":"35102319","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":[]}