ArticleThe Journal of biological chemistry2015
Transcription factors GATA4 and HNF4A control distinct aspects of intestinal homeostasis in conjunction with transcription factor CDX2.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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Who cites it
45 citing papers in PubMed, 81 citations in OpenAlex.
- Dynamics and master transcription factors dependence of intestinal super-enhancers during differentiation and oncogenesis.Nucleic acids research · 2026Article
- Dynamic Reprogramming of PDGFRA-Expressing Stromal Cells Facilitates WNT-Driven Transformation by Promoting a Fetal-Like State in the Intestinal Epithelium.Cancer research · 2026Article
- Opposing lineage specifiers induce a protumor hybrid identity state in lung adenocarcinoma.Genes & development · 2025Article
- Dynamic Reprogramming of Stromal Pdgfra-expressing cells during WNT-Mediated Transformation of the Intestinal Epithelium.bioRxiv : the preprint server for biology · 2025Article
- PMF-GRN: a variational inference approach to single-cell gene regulatory network inference using probabilistic matrix factorization.Genome biology · 2024Article
- Tissue-location-specific transcription programs drive tumor dependencies in colon cancer.Nature communications · 2024Article
- Transcriptional regulation of metabolism in the intestinal epithelium.American journal of physiology. Gastrointestinal and liver physiology · 2023Review
- Article
- Transcriptional and epigenomic profiling identifies YAP signaling as a key regulator of intestinal epithelium maturation.Science advances · 2023Article
- Forkhead box protein D2 suppresses colorectal cancer by reprogramming enhancer interactions.Nucleic acids research · 2023Article
- EPIREGULIN creates a developmental niche for spatially organized human intestinal enteroids.JCI insight · 2023Article
- Be like water, my cells: cell plasticity and the art of transformation.Frontiers in cell and developmental biology · 2023Review
- Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine.Frontiers in endocrinology · 2023Review
- Enterotoxigenic Escherichia coli heat-labile toxin drives enteropathic changes in small intestinal epithelia.Nature communications · 2022Article
- Article
- CDX2-induced intestinal metaplasia in human gastric organoids derived from induced pluripotent stem cells.iScience · 2022Article
- Starvation causes changes in the intestinal transcriptome and microbiome that are reversed upon refeeding.BMC genomics · 2022Article
- Transcription factor-mediated intestinal metaplasia and the role of a shadow enhancer.Genes & development · 2022Article
- Transcriptional Integration of Distinct Microbial and Nutritional Signals by the Small Intestinal Epithelium.Cellular and molecular gastroenterology and hepatology · 2022Article
- Src family kinases inhibit differentiation of intestinal epithelial cells through the Hippo effector YAP1.Biology open · 2021Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.