{"doi":"10.7554/elife.96028","title":"Transcription factor condensates, 3D clustering, and gene expression enhancement of the MET regulon","abstract":"Some transcription factors (TFs) can form liquid–liquid phase separated (LLPS) condensates. However, the functions of these TF condensates in 3-Dimentional (3D) genome organization and gene regulation remain elusive. In response to methionine (met) starvation, budding yeast TF Met4 and a few co-activators, including Met32, induce a set of genes involved in met biosynthesis. Here, we show that the endogenous Met4 and Met32 form co-localized puncta-like structures in yeast nuclei upon met depletion. Recombinant Met4 and Met32 form mixed droplets with LLPS properties in vitro. In relation to chromatin, Met4 puncta co-localize with target genes, and at least a subset of these target genes is clustered in 3D in a Met4-dependent manner. A MET3pr -GFP reporter inserted near several native Met4-binding sites becomes co-localized with Met4 puncta and displays enhanced transcriptional activity. A Met4 variant with a partial truncation of an intrinsically disordered region (IDR) shows less puncta formation, and this mutant selectively reduces the reporter activity near Met4-binding sites to the basal level. Overall, these results support a model where Met4 and co-activators form condensates to bring multiple target genes into a vicinity with higher local TF concentrations, which facilitates a strong response to methionine depletion.","journal":"eLife","year":2024,"id":454454,"datarank":0.384547142629041,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.07263091137706555,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.07263091137706555,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":6,"citers_with_citation_signal":6,"citers_with_endowment":6,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE252386"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":650875,"name":"Leman Simpson","orcid":null,"position":1,"is_corresponding":false},{"id":1277646,"name":"Yi Li","orcid":"0000-0002-2309-0163","position":2,"is_corresponding":false},{"id":1277647,"name":"Samuel Becker","orcid":"0000-0001-6007-5221","position":3,"is_corresponding":false},{"id":569164,"name":"Fan Zou","orcid":"0000-0003-3765-1176","position":4,"is_corresponding":false},{"id":650347,"name":"Xin Zhang","orcid":"0000-0002-1119-9399","position":5,"is_corresponding":false},{"id":447230,"name":"Lu Bai","orcid":"0000-0003-3667-2944","position":6,"is_corresponding":false},{"id":1277645,"name":"James Lee","orcid":"0009-0003-9935-1301","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T02:03:07.923686Z","pmid":"39347738","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":[]}