{"doi":"10.1073/pnas.062041099","title":"The embryonic stem cell transcription factors Oct-4 and FoxD3 interact to regulate endodermal-specific promoter expression","abstract":"<jats:p>The POU homeodomain protein Oct-4 and the Forkhead Box protein FoxD3 (previously Genesis) are transcriptional regulators expressed in embryonic stem cells. Down-regulation of Oct-4 during gastrulation is essential for proper endoderm development. After gastrulation, FoxD3 is generally down-regulated during early endoderm formation, although it specifically remains expressed in the embryonic neural crest. In these studies, we have found that Oct-4 and FoxD3 can bind to identical regulatory DNA sequences. In addition, Oct-4 physically interacted with the FoxD3 DNA-binding domain. Cotransfection of Oct-4 and FoxD3 expression vectors activated the osteopontin enhancer, which is expressed in totipotent embryonic stem cells. FoxA1 and FoxA2 (previously HNF-3α and HNF-3β) are Forkhead Box transcription factors that participate in liver and lung formation from foregut endoderm. Although FoxD3 activated the FoxA1 and FoxA2 promoters, Oct-4 inhibited FoxD3 activation of the FoxA1 and FoxA2 endodermal promoters. These data indicate that Oct-4 functions as a corepressor of FoxD3 to provide embryonic lineage-specific transcriptional regulatory activity to maintain appropriate developmental timing.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2002,"id":638791,"datarank":0.7612760722850741,"base_score":5.075173815233827,"endowment":5.075173815233827,"self_citation_contribution":0.7612760722850741,"citation_network_contribution":0.0,"self_endowment_contribution":0.7612760722850741,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":159,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1659398,"name":"Robert Costa","orcid":null,"position":1,"is_corresponding":false},{"id":1659399,"name":"Heather Ramsey","orcid":null,"position":2,"is_corresponding":false},{"id":1659400,"name":"Trevor Starnes","orcid":null,"position":3,"is_corresponding":false},{"id":1659401,"name":"Gail Vance","orcid":null,"position":4,"is_corresponding":false},{"id":1659402,"name":"Kent Robertson","orcid":null,"position":5,"is_corresponding":false},{"id":1162385,"name":"Mark Kelley","orcid":"0009-0003-9436-5595","position":6,"is_corresponding":false},{"id":1659403,"name":"Rolland Reinbold","orcid":null,"position":7,"is_corresponding":false},{"id":1659404,"name":"Hans Scholer","orcid":null,"position":8,"is_corresponding":false},{"id":240060,"name":"Robert Hromas","orcid":"0000-0002-1916-6276","position":9,"is_corresponding":false},{"id":1140078,"name":"Ying Guo","orcid":"0000-0002-6429-9297","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The embryonic stem cell transcription factors Oct-4 and FoxD3 interact to regulate endodermal-specific promoter expression","abstract":"<jats:p>The POU homeodomain protein Oct-4 and the Forkhead Box protein FoxD3 (previously Genesis) are transcriptional regulators expressed in embryonic stem cells. Down-regulation of Oct-4 during gastrulation is essential for proper endoderm development. After gastrulation, FoxD3 is generally down-regulated during early endoderm formation, although it specifically remains expressed in the embryonic neural crest. In these studies, we have found that Oct-4 and FoxD3 can bind to identical regulatory DNA sequences. In addition, Oct-4 physically interacted with the FoxD3 DNA-binding domain. Cotransfection of Oct-4 and FoxD3 expression vectors activated the osteopontin enhancer, which is expressed in totipotent embryonic stem cells. FoxA1 and FoxA2 (previously HNF-3α and HNF-3β) are Forkhead Box transcription factors that participate in liver and lung formation from foregut endoderm. Although FoxD3 activated the FoxA1 and FoxA2 promoters, Oct-4 inhibited FoxD3 activation of the FoxA1 and FoxA2 endodermal promoters. These data indicate that Oct-4 functions as a corepressor of FoxD3 to provide embryonic lineage-specific transcriptional regulatory activity to maintain appropriate developmental timing.</jats:p>","is_dataset_classified":null,"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":"11891324","pmcid":"PMC122580","openalex_id":null,"authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"P01 CA74295","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HL48914","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM043241","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM43241","title":null}],"total_grants":4,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/122580","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.062041099","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Cell Line","Stem Cells","Endoderm","Humans","Sialoglycoproteins","DNA-Binding Proteins","Nuclear Proteins","Transcription Factors","Repressor Proteins","DNA","Transfection","Gene Expression Regulation, Developmental","Binding Sites","Protein Structure, Tertiary","Protein Binding","Substrate Specificity","Cell Lineage","Octamer Transcription Factor-3","Hepatocyte Nuclear Factor 3-beta","Osteopontin","Enhancer Elements, Genetic","Promoter Regions, Genetic"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T21:32:11.083196Z","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":[]}