{"doi":"10.1242/dev.204924","title":"Functional dissection of H3K4 methyltransferases reveals distinct catalytic and non-catalytic roles in <i>C. elegans</i> development","abstract":"The KMT2 class of histone methyltransferases regulates methylation of histone 3 lysine 4 (H3K4), a conserved post-translational modification associated with active transcription. However, previous studies have highlighted catalytic-independent functions of KMT2 members and questioned the influence of H3K4 methylation on gene expression. Here, we address this by generating catalytically inactive mutants of SET-2 and SET-16, the two KMT2 members in Caenorhabditis elegans. Through chromatin analysis, we determined the effect of SET-2 and SET-16 catalytic activities on H3K4me3 deposition and identified shared and distinct targets. Gene expression profiling showed that simultaneous inactivation of SET-2 and SET-16 catalytic activities results in gene deregulation independent of H3K4me3 status at transcription start sites. Finally, we examined the relevance of SET-2 and SET-16 catalytic activity on phenotypes identified in null mutants and found that SET-2 catalytic activity is essential for proper somatic development, whereas SET-16 enzymatic activity has cell type-specific roles. Interestingly, animals lacking SET-2 and SET-16 catalytic activity are viable and fertile under normal growth conditions. Our results reveal catalytic-dependent and -independent roles of KMT2 members, and that combined loss of SET-16 and SET-2 is compatible with life in C. elegans.","journal":"Development","year":2025,"id":547859,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9612,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":649378,"name":"Hua Wang","orcid":"0000-0002-1424-0270","position":1,"is_corresponding":false},{"id":740584,"name":"Katrine Madsen","orcid":null,"position":2,"is_corresponding":false},{"id":1136759,"name":"Mandoh Zeijdner","orcid":"0000-0002-7427-9345","position":3,"is_corresponding":false},{"id":266716,"name":"Kristian Helin","orcid":"0000-0003-1975-6097","position":4,"is_corresponding":false},{"id":406558,"name":"Steffen Nørgaard","orcid":"0000-0002-0094-8112","position":5,"is_corresponding":false},{"id":406561,"name":"Anna Elisabetta Salcini","orcid":"0000-0001-5828-2512","position":6,"is_corresponding":false},{"id":406559,"name":"Benedetta Attianese","orcid":"0000-0002-7760-1731","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-19T02:53:53.962932Z","pmid":"41122790","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":[]}