{"doi":"10.1074/jbc.m114.620211","title":"Transcription Factors GATA4 and HNF4A Control Distinct Aspects of Intestinal Homeostasis in Conjunction with Transcription Factor CDX2","abstract":null,"journal":"Journal of Biological Chemistry","year":2015,"id":623675,"datarank":2.6003678362048364,"base_score":4.430816798843313,"endowment":4.430816798843313,"self_citation_contribution":0.6646225198264971,"citation_network_contribution":1.9357453163783394,"self_endowment_contribution":0.6646225198264971,"citer_contribution":1.9357453163783394,"corpus_percentile":null,"corpus_rank":null,"citation_count":83,"citer_count":60,"citers_with_citation_signal":53,"citers_with_endowment":53,"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":705187,"name":"Boaz E. Aronson","orcid":"0000-0001-8682-5190","position":1,"is_corresponding":false},{"id":1611920,"name":"Stephen D. Krasinski","orcid":null,"position":2,"is_corresponding":false},{"id":71354,"name":"Ramesh A. Shivdasani","orcid":"0000-0002-2828-1727","position":3,"is_corresponding":false},{"id":241177,"name":"Michael P. Verzi","orcid":"0000-0003-4082-4330","position":4,"is_corresponding":false},{"id":806475,"name":"Adrianna K. San Roman","orcid":"0000-0003-4511-3052","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Transcription Factors GATA4 and HNF4A Control Distinct Aspects of Intestinal Homeostasis in Conjunction with Transcription Factor CDX2","abstract":"Distinct groups of transcription factors (TFs) assemble at tissue-specific cis -regulatory sites, implying that different TF combinations may control different genes and cellular functions. Within such combinations, TFs that specify or maintain a lineage and are therefore considered master regulators may play a key role. Gene enhancers often attract these tissue-restricted TFs, as well as TFs that are expressed more broadly. However, the contributions of the individual TFs to combinatorial regulatory activity have not been examined critically in many cases in vivo . We address this question using a genetic approach in mice to inactivate the intestine-specifying and intestine-restricted factor CDX2 alone or in combination with its more broadly expressed partner factors, GATA4 and HNF4A. Compared with single mutants, each combination produced significantly greater defects and rapid lethality through distinct anomalies. Intestines lacking Gata4 and Cdx2 were deficient in crypt cell replication, whereas combined loss of Hnf4a and Cdx2 specifically impaired viability and maturation of villus enterocytes. Integrated analysis of TF binding and of transcripts affected in Hnf4a ; Cdx2 compound-mutant intestines indicated that this TF pair controls genes required to construct the apical brush border and absorb nutrients, including dietary lipids. This study thus defines combinatorial TF activities, their specific requirements during tissue homeostasis, and modules of transcriptional targets in intestinal epithelial cells in vivo .Different transcription factor combinations may control distinct or overlapping cellular functions. Results Intestines lacking tissue-restricted CDX2 and broadly expressed GATA4 or HNF4A show unique defects. Conclusion Combined with CDX2, GATA4 controls crypt cell replication, whereas HNF4A regulates enterocyte maturation and a cohort of functional enterocyte genes. Significance Combinatorial mechanisms for intestine-specific gene regulation may apply generally to other tissues.","is_dataset_classified":null,"base_score":4.430816798843313,"endowment":4.430816798843313,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25488664","pmcid":"PMC4340426","openalex_id":"https://openalex.org/W1992570553","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"R01DK08229","title":null},{"funder_name":"National Institutes of Health","grant_id":"R01DK061382","title":null},{"funder_name":"National Institutes of Health","grant_id":"F31CA180784","title":null},{"funder_name":"National Institutes of Health","grant_id":"K01DK088868","title":null},{"funder_name":"National Institutes of Health","grant_id":"P50CA127003","title":null}],"total_grants":5,"fwci":2.1323,"citation_percentile":0.87290274,"influential_citations":0,"citation_trend":[{"year":2015,"count":1},{"year":2016,"count":3},{"year":2017,"count":6},{"year":2018,"count":9},{"year":2019,"count":11},{"year":2020,"count":6},{"year":2021,"count":6},{"year":2022,"count":11},{"year":2023,"count":11},{"year":2024,"count":14},{"year":2025,"count":2},{"year":2026,"count":3}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.jbc.org/article/S0021925820578381/pdf","host_type":"journal"},{"url":"http://www.jbc.org/article/S0021925820578381/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820578381?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820578381?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.M114.620211","host_type":"publisher"},{"url":"https://doi.org/10.1074/jbc.m114.620211","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25488664","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4340426","host_type":"repository"}],"fields_of_study":["Digestive system and related health","RNA modifications and cancer","Epigenetics and DNA Methylation","Amino Acid Motifs","Animals","Binding Sites","CDX2 Transcription Factor","Cell Differentiation","Chromatin Immunoprecipitation","Enterocytes","GATA4 Transcription Factor","Gene Expression Profiling","Gene Expression Regulation","Hepatocyte Nuclear Factor 4","Homeodomain Proteins","Intestinal Mucosa","Mice","Mice, Transgenic","Oligonucleotide Array Sequence Analysis","Transcription Factors"],"mesh_terms":["CDX2 Transcription Factor","Animals","Binding Sites","Cell Differentiation","Gene Expression Regulation","Intestinal Mucosa","Mice, Transgenic","Transcription Factors","Homeodomain Proteins","Oligonucleotide Array Sequence Analysis","Amino Acid Motifs","Gene Expression Profiling","Enterocytes","Chromatin Immunoprecipitation","GATA4 Transcription Factor","Mice","Hepatocyte Nuclear Factor 4"],"keywords":["Transcription factor","CDX2","Biology","Cell biology","Enhancer","GATA transcription factor","Genetics","GATA4","Gene","Homeobox","Gene expression","Promoter","Cell proliferation","Cell differentiation","Gene regulation","lipid metabolism","intestinal epithelium","Cdx2 Transcription Factor","Hnf4a Transcription Factor"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T00:50:59.678667Z","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":[]}