{"doi":"10.1371/journal.pbio.3002980","title":"SUMO-mediated regulation of H3K4me3 reader SET-26 controls germline development in C. elegans","abstract":"Sumoylation is a posttranslational modification essential for multiple cellular functions in eukaryotes. ULP-2 is a conserved SUMO protease required for embryonic development in Caenorhabditis elegans. Here, we revealed that ULP-2 controls germline development by regulating the PHD-SET domain protein, SET-26. Specifically, loss of ULP-2 results in sterility and a progressive elevation of global protein sumoylation. In the germline of ulp-2 null mutant, meiosis is arrested at the diplotene stage and the cells in the proximal germline acquire a somatic fate. Germline RNAseq analysis revealed the down-regulation of numerous germline genes in ulp-2 mutants, whereas somatic gene expression is up-regulated. To determine the key factors that are regulated by ULP-2, we performed a yeast two-hybrid screen and identified the histone methylation reader, SET-26 as a ULP-2 interacting protein. Loss of SET-26 enhanced the sterility of ulp-2 mutant animals. Consistently, SET-26 is sumoylated and its sumoylation levels are regulated by ULP-2. Moreover, we detected a reduction in H3K4 tri-methylation (H3K4me3) histone levels bound to SET-26 in the ulp-2 mutant background suggesting a dependence of this histone reader on balanced sumoylation. Finally, a comparative proteomics screen between WT and ulp-2 loss of activity identified the predicted methyltransferase SET-27 as a ULP-2-dependent SET-26-associated protein. SET-27 knockout genetically interacts with ULP-2 in the germline, but not with SET-26. Taken together, we revealed a SUMO protease/H3K4me3 histone reader axis which is required for the maintenance and regulation of germline development.","journal":"PLoS Biology","year":2025,"id":531765,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"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":1276198,"name":"Ulrike Bening Abu‐Shach","orcid":null,"position":1,"is_corresponding":false},{"id":1341352,"name":"Asha Raju","orcid":null,"position":2,"is_corresponding":false},{"id":761946,"name":"Zlata Vershinin","orcid":"0000-0002-0060-693X","position":3,"is_corresponding":false},{"id":24803,"name":"Dan Levy","orcid":"0000-0003-0719-0305","position":4,"is_corresponding":false},{"id":337003,"name":"Mike Boxem","orcid":"0000-0003-3966-4173","position":5,"is_corresponding":false},{"id":801122,"name":"Limor Broday","orcid":"0000-0002-3864-0500","position":6,"is_corresponding":false},{"id":1275802,"name":"Cátia A. Carvalho","orcid":"0000-0001-7810-9127","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T02:51:18.928280Z","pmid":"39761316","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":[]}