{"doi":"10.1101/2025.07.29.667167","title":"A cryptic START domain regulates deeply conserved transcription factors","abstract":"Transcription factors (TFs) integrate a diverse array of inputs to achieve the exquisite control of gene expression necessary for life. In plants, this is exemplified by the deeply conserved CLASS III HOMEODOMAIN LEUCINE ZIPPER (HD-ZIPIII) family of TFs. HD-ZIPIII activity is controlled by inputs at transcriptional, post-transcriptional, and post-translational levels. As part of their multidomain architecture, HD-ZIPIII TFs contain a StAR-related lipid transfer (START) domain, a ubiquitously distributed evolutionary module that binds various types of lipophilic ligands. Here, we show that HD-ZIPIII and HD-ZIPIV proteins contain a cryptic, deeply conserved START domain which we term the disorder-containing START domain (dSTART). The dSTART domain is required for HD-ZIPIII developmental function, controlling their subcellular localization and DNA-binding properties. The dSTART domain also helps discriminate responsive from non-responsive binding sites across the HD-ZIPIII shared genetic network. Finally, we identify candidate ligands of the dSTART domain including several species of phosphatidylglycerol and phosphatidic acid. The identification and functional characterization of a cryptic START domain provides new mechanistic insights into a deeply conserved family of TFs with roles in nearly all aspects of plant development.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":558655,"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":0.9563,"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":666798,"name":"Ekaterina P. Andrianova","orcid":"0000-0003-3719-0293","position":1,"is_corresponding":false},{"id":557249,"name":"Brian J. Smith","orcid":"0000-0002-7091-3046","position":2,"is_corresponding":false},{"id":997661,"name":"Nicole I. Callery","orcid":null,"position":3,"is_corresponding":false},{"id":1372720,"name":"Dominic Kolonay","orcid":null,"position":4,"is_corresponding":false},{"id":379236,"name":"Ashton S. Holub","orcid":"0000-0002-9443-8358","position":5,"is_corresponding":false},{"id":1186878,"name":"Ricardo A. Urquidi Camacho","orcid":"0000-0002-5526-3938","position":6,"is_corresponding":false},{"id":1005229,"name":"Sarah G. Choudury","orcid":"0000-0003-2564-434X","position":7,"is_corresponding":false},{"id":1382537,"name":"I. J. Higgins","orcid":"0009-0003-5770-8739","position":8,"is_corresponding":false},{"id":317405,"name":"Igor B. Zhulin","orcid":"0000-0002-6708-5323","position":9,"is_corresponding":false},{"id":379237,"name":"Aman Y. Husbands","orcid":"0000-0003-4580-1779","position":10,"is_corresponding":false},{"id":993541,"name":"Courtney E. Dresden","orcid":"0000-0002-8815-7226","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T02:55:30.312295Z","pmid":"40766543","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":[]}