{"doi":"10.1101/gad.353393.125","title":"Nuclear receptor coregulator interactions: beyond the switch","abstract":"Nuclear receptors (NRs) are ligand-regulated transcription factors (TFs) that respond to hormonal, nutritional, and environmental signals. NRs as druggable targets are known for their therapeutic potential in treating a wide range of diseases, including metabolic disorders, inflammatory conditions, and various cancers. Due to their structure and ability to interact with DNA, ligands, and other proteins, NR transcriptional regulatory capacity is fine-tuned through dynamic interactions with a disparate array of coregulators, including coactivators and corepressors that form an intricate network that integrates multiple signaling and metabolic pathways. This review synthesizes insights into the functional interactions between NRs and the modulators of transcription, focusing on interactions between NRs and coregulators and how their model of interaction has evolved from a binary switch to a coregulator shift mechanism in regulating ligand-dependent transcription. These nuanced multifaceted interactions collectively direct dynamic gene expression by NRs across multiple tissues in physiology and diseases.","journal":"Genes & Development","year":2025,"id":7175,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.043,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-12-18","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":39746,"name":"Mitchell A. Lazar","orcid":"0000-0001-8653-1280","position":1,"is_corresponding":false},{"id":64840,"name":"Fathima N. Cassim Bawa","orcid":"0000-0002-6766-0965","position":2,"is_corresponding":false},{"id":64839,"name":"F. Nafrisha Cassim Bawa","orcid":null,"position":0,"is_corresponding":true}],"reference_count":217,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"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":[]}