{"doi":"10.1016/j.devcel.2023.08.006","title":"A circadian-like gene network programs the timing and dosage of heterochronic miRNA transcription during C. elegans development","abstract":"Development relies on the exquisite control of both the timing and the levels of gene expression to achieve robust developmental transitions. How cis- and trans-acting factors control both aspects simultaneously is unclear. We show that transcriptional pulses of the temporal patterning microRNA (miRNA) lin-4 are generated by two nuclear hormone receptors (NHRs) in C. elegans, NHR-85 and NHR-23, whose mammalian orthologs, Rev-Erb and ROR, function in the circadian clock. Although Rev-Erb and ROR antagonize each other to control once-daily transcription in mammals, NHR-85/NHR-23 heterodimers bind cooperatively to lin-4 regulatory elements to induce a single pulse of expression during each larval stage. Each pulse's timing, amplitude, and duration are dictated by the phased expression of these NHRs and the C. elegans Period ortholog, LIN-42, that binds to and represses NHR-85. Therefore, during nematode temporal patterning, an evolutionary rewiring of circadian clock components couples the timing of gene expression to the control of transcriptional dosage.","journal":"Developmental Cell","year":2023,"id":320643,"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":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1032585,"name":"Shubham Sahu","orcid":null,"position":1,"is_corresponding":false},{"id":467178,"name":"Natalia Stec","orcid":"0000-0003-0465-9390","position":2,"is_corresponding":false},{"id":467179,"name":"Kelly Hills-Muckey","orcid":"0000-0002-2475-6801","position":3,"is_corresponding":false},{"id":1023274,"name":"Dexter W. Adams","orcid":null,"position":4,"is_corresponding":false},{"id":362127,"name":"Jing Wang","orcid":"0000-0003-4615-661X","position":5,"is_corresponding":false},{"id":474517,"name":"M. Jaremko","orcid":"0000-0002-0340-4452","position":6,"is_corresponding":false},{"id":335006,"name":"Leemor Joshua‐Tor","orcid":"0000-0001-8185-8049","position":7,"is_corresponding":false},{"id":467181,"name":"Wolfgang W. Keil","orcid":"0000-0002-8176-8585","position":8,"is_corresponding":false},{"id":467182,"name":"Christopher M. Hammell","orcid":"0000-0002-5961-0976","position":9,"is_corresponding":false},{"id":479328,"name":"Brian A. Kinney","orcid":"0000-0001-5628-1436","position":0,"is_corresponding":true}],"reference_count":104,"raw_metadata":null,"created_at":"2026-07-19T01:07:27.434133Z","pmid":"37643611","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":[]}