{"doi":"10.1530/jme-12-0097","title":"The ligand-mediated nuclear mobility and interaction with estrogen-responsive elements of estrogen receptors are subtype specific","abstract":"17β-Estradiol (E2) plays important roles in functions of many tissues. E2 effects are mediated by estrogen receptor (ER) α and β. ERs regulate transcriptions through estrogen-responsive element (ERE)-dependent and ERE-independent modes of action. ER binding to ERE constitutes the basis of the ERE-dependent pathway. Direct/indirect ER interactions with transcription complexes define ERE-independent signaling. ERs share functional features. Ligand-bound ERs nevertheless induce distinct transcription profiles. Live cell imaging indicates a dynamic nature of gene expressions by highly mobile ERs. However, the relative contribution of ER mobility at the ERE-independent pathway to the overall kinetics of ER mobility remains undefined. We used fluorescent recovery after a photo-bleaching approach to assess the ligand-mediated mobilities of ERE binding-defective ERs, EREBD. The decrease in ERα mobility with E2 or the selective ER modulator 4-hydroxyl-tamoxifen (4HT) was largely due to the interaction of the receptor with ERE. Thus, ERα bound to E2 or 4HT mediates transcriptions from the ERE-independent pathway with remarkably fast kinetics that contributes fractionally to the overall motility of the receptor. The antagonist Imperial Chemical Industries 182 780 immobilized ERαs. The mobilities of ERβ and ERβEBD in the presence of ligands were indistinguishable kinetically. Thus, ERβ mobility is independent of the nature of ligands and the mode of interaction with target sites. Chimeric ERs indicated that the carboxyl-termini are critical regions for subtype-specific mobility. Therefore, while ERs are highly mobile molecules interacting with target sites with fast kinetics, an indication of the hit-and-run model of transcription, they differ mechanistically to modulate transcriptions.","journal":"Journal of Molecular Endocrinology","year":2012,"id":23443,"datarank":0.7455434482633085,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.3496848488210196,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.3496848488210196,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":9,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":143915,"name":"Linda M Callahan","orcid":null,"position":1,"is_corresponding":false},{"id":143916,"name":"Yanfang Huang","orcid":null,"position":2,"is_corresponding":false},{"id":143917,"name":"Andrew J Lee","orcid":null,"position":3,"is_corresponding":false},{"id":143914,"name":"Mesut Muyan","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23014840","pmcid":"PMC3674415","openalex_id":null,"authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"CA113682","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA113682","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01CA113682-05","title":"Toward a transcription therapy for breast cancer"}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":"CC BY NC ND","oa_locations":[{"url":"https://jme.bioscientifica.com/downloadpdf/journals/jme/49/3/249.pdf","host_type":"publisher"},{"url":"https://jme.bioscientifica.com/view/journals/jme/49/3/249.xml","host_type":"publisher"},{"url":"https://jme.bioscientifica.com/downloadpdf/journals/jme/49/3/249.xml","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3674415","host_type":"repository"},{"url":"https://doi.org/10.1530/jme-12-0097","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/23014840","host_type":""},{"url":"https://dx.doi.org/10.1530/jme-12-0097","host_type":""},{"url":"https://hdl.handle.net/11511/36061","host_type":""}],"fields_of_study":["0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Cell Line, Tumor","Hela Cells","Cell Nucleus","Humans","Green Fluorescent Proteins","Receptors, Estrogen","Blotting, Western","Electrophoretic Mobility Shift Assay","Chromatin Immunoprecipitation","Response Elements","Protein Binding","Protein Transport"],"keywords":["Cell Nucleus","Chromatin Immunoprecipitation","Signaling pathways","Blotting, Western","Green Fluorescent Proteins","Breast-cancer cells","Beta","Activation","Electrophoretic Mobility Shift Assay","Response Elements","DNA-binding","Protein Transport","Receptors, Estrogen","Transcriptional responses","Cell Line, Tumor","Coactivator","Humans","Gene-expression","Recruitment","Er-alpha","HeLa Cells","Protein Binding"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T19:29:25.295355Z","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":[]}