{"doi":"10.1210/me.2002-0399","title":"Liver X Receptors Interact with Corepressors to Regulate Gene Expression","abstract":"<jats:title>Abstract</jats:title><jats:p>Liver X receptors (LXRs) are members of the nuclear receptor superfamily that regulate gene expression in response to oxysterols and play a critical role in cholesterol homeostasis by regulating genes that are involved in cholesterol transport, catabolism, and triglyceride synthesis. Oxysterols and synthetic agonists bind LXRs and activate transcription by recruiting coactivator proteins. The role of LXRs in regulating target gene expression in the absence of ligand is unknown. Here we show that LXRs interact with corepressors, N-CoR (nuclear receptor corepressor) and SMRT (silent mediator of retinoic acid receptor and thyroid receptor), which are released upon binding agonists. The LXR-corepressor interaction is isoform selective, wherein LXRα has a very strong interaction with corepressors and LXRβ only shows weak interaction. LXRs also exhibit a preference for interacting with N-CoR vs. SMRT. Similar to other nuclear receptors, mutations in the LXR helix 3 and 4 region abolish corepressor interaction. Using a transient transfection assay, we demonstrate that LXR represses transcription that can be further increased by cotransfecting N-CoR into cells. Chromatin immunoprecipitation experiments further indicated that N-CoR is recruited onto endogenous LXR target genes, and addition of LXR agonists releases N-CoR from their promoters. Collectively, these results suggest that corepressors play an important role in regulating LXR target gene expression.</jats:p>","journal":"Molecular Endocrinology","year":2003,"id":24777,"datarank":6.657177984115403,"base_score":5.049856007249537,"endowment":5.049856007249537,"self_citation_contribution":0.7574784010874307,"citation_network_contribution":5.899699583027973,"self_endowment_contribution":0.7574784010874307,"citer_contribution":5.899699583027973,"corpus_percentile":null,"corpus_rank":null,"citation_count":155,"citer_count":153,"citers_with_citation_signal":129,"citers_with_endowment":129,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":147674,"name":"Suzhen Li","orcid":null,"position":1,"is_corresponding":false},{"id":71438,"name":"Jun Wu","orcid":"0000-0002-3381-2561","position":2,"is_corresponding":false},{"id":147675,"name":"Chunsheng Xia","orcid":null,"position":3,"is_corresponding":false},{"id":147676,"name":"Deepak S. Lala","orcid":null,"position":4,"is_corresponding":false},{"id":111536,"name":"Xiao Hu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.049856007249537,"endowment":5.049856007249537,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12663743","pmcid":null,"openalex_id":"https://openalex.org/W2112555162","authors":[],"funders":[],"total_grants":0,"fwci":11.6874,"citation_percentile":0.98845841,"influential_citations":13,"citation_trend":[{"year":2012,"count":7},{"year":2013,"count":9},{"year":2014,"count":6},{"year":2015,"count":8},{"year":2016,"count":5},{"year":2017,"count":6},{"year":2018,"count":4},{"year":2019,"count":6},{"year":2020,"count":8},{"year":2021,"count":2},{"year":2022,"count":3},{"year":2023,"count":4},{"year":2024,"count":9},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://academic.oup.com/mend/article-pdf/17/6/1019/8964217/mend1019.pdf","host_type":"journal"},{"url":"https://academic.oup.com/mend/article-pdf/17/6/1019/8964217/mend1019.pdf","host_type":"BRONZE"},{"url":"https://academic.oup.com/mend/article-pdf/17/6/1019/8964217/mend1019.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/mend/article-pdf/17/6/1019/8964217/mend1019.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1210/me.2002-0399","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12663743","host_type":"repository"}],"fields_of_study":["Cholesterol and Lipid Metabolism","Drug Transport and Resistance Mechanisms","Peroxisome Proliferator-Activated Receptors","Medicine","Biology","Animals","Cells, Cultured","DNA-Binding Proteins","Gene Expression Regulation","Humans","Liver X Receptors","Nuclear Proteins","Nuclear Receptor Co-Repressor 1","Nuclear Receptor Co-Repressor 2","Orphan Nuclear Receptors","Protein Binding","Protein Isoforms","Receptors, Cytoplasmic and Nuclear","Repressor Proteins","Transcription, Genetic"],"mesh_terms":["Liver X Receptors","Animals","Cells, Cultured","DNA-Binding Proteins","Gene Expression Regulation","Humans","Nuclear Proteins","Protein Binding","Repressor Proteins","Transcription, Genetic","Receptors, Cytoplasmic and Nuclear","Protein Isoforms","Nuclear Receptor Co-Repressor 1","Nuclear Receptor Co-Repressor 2","Orphan Nuclear Receptors"],"keywords":["Corepressor","Liver X receptor","Nuclear receptor","Biology","Nuclear receptor co-repressor 1","Coactivator","Small heterodimer partner","Chromatin immunoprecipitation","Retinoid X receptor","Cell biology","Transcription factor","Regulation of gene expression","Liver receptor homolog-1","Promoter","Gene expression","Biochemistry","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T23:13:14.692082Z","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,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}