ArticleProceedings of the National Academy of Sciences of the United States of America2001
A transcription factor regulatory circuit in differentiated pancreatic cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 4 of them syntheses that pooled it.
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Who cites it
103 citing papers in PubMed, 4 syntheses or guidelines pooled it, 255 citations in OpenAlex.
- Pregnancy and Neonatal Outcomes in Maturity-Onset Diabetes of the Young: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.Nature communications · 2018Pooled it
- Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms.Human molecular genetics · 2016Pooled it
- Prediabetes is associated with HNF-4 α P2 promoter polymorphism rs1884613: a case-control study in Han Chinese population and an updated meta-analysis.Disease markers · 2014Pooled it
- FOXA2 in islet biology: Orchestrating pancreatic development and glucose homeostasis.Genes & diseases · 2026Review
- Defective HNF1A hinders GLI3 processing favoring duodenal versus pancreatic fate, thus leading to intestinal elongation in vivo.Genes & development · 2026Article
- Systemic control of HNF1B-driven redox homeostasis by N6-adenosine methylation.Nucleic acids research · 2026Article
- Bridging pancreatic and hepatic development: overlapping genes and their role in diabetes.Cellular & molecular biology letters · 2025Review
- HNF1A and A1CF coordinate a beta cell transcription-splicing axis that is disrupted in type 2 diabetes.Cell metabolism · 2025Article
- The age-dependent regulation of pancreatic islet landscape is fueled by a HNF1a-immune signaling loop.Mechanisms of ageing and development · 2024Article
- Molecular mechanism of HNF-1A-mediated HNF4A gene regulation and promoter-driven HNF4A-MODY diabetes.JCI insight · 2024Article
- Repression of latent NF-κB enhancers by PDX1 regulates β cell functional heterogeneity.Cell metabolism · 2024Article
- Promoter Methylation Leads to Hepatocyte Nuclear Factor 4A Loss and Pancreatic Cancer Aggressiveness.Gastro hep advances · 2024Article
- Role ofBiomedicines · 2023Article
- The protein architecture and allosteric landscape of HNF4α.Frontiers in endocrinology · 2023Review
- Novel Loss-of-Function Variant in HNF1a Induces β-Cell Dysfunction through Endoplasmic Reticulum Stress.International journal of molecular sciences · 2022Article
- Ebola virus infection induces a delayed type I IFN response in bystander cells and the shutdown of key liver genes in human iPSC-derived hepatocytes.Stem cell reports · 2022Article
- The HASTER lncRNA promoter is a cis-acting transcriptional stabilizer of HNF1A.Nature cell biology · 2022Article
- Variants influencing age at diagnosis of HNF1A-MODY.Molecular medicine (Cambridge, Mass.) · 2022Article
- HNF1A Mutations and Beta Cell Dysfunction in Diabetes.International journal of molecular sciences · 2022Review
43 more citing papers are in PubMed but not listed here.
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4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the human genes encoding hepatocyte nuclear factors (HNF) 1alpha, 1beta, 4alpha, and IPF1(PDX1/IDX1/STF1) result in pancreatic beta cell dysfunction and diabetes mellitus. In hepatocytes, hnf4alpha controls the transcription of hnf1alpha, suggesting that this same interaction may operate in beta cells and thus account for the common diabetic phenotype. We show that, in pancreatic islet and exocrine cells, hnf4alpha expression unexpectedly depends on hnf1alpha. This effect is tissue-specific and mediated through direct occupation by hnf1alpha of an alternate promoter located 45.6 kb from the previously characterized hnf4alpha promoter. Hnf1alpha also exerts direct control of pancreatic-specific expression of hnf4gamma and hnf3gamma. Hnf1alpha dependence of hnf4alpha, hnf4gamma, hnf3gamma, and two previously characterized distal targets (glut2 and pklr) is established only after differentiated cells arise during pancreatic embryonic development. These studies define an unexpected hierarchical regulatory relationship between two genes involved in human monogenic diabetes in the cells, which are relevant to its pathophysiology. Furthermore, they indicate that hnf1alpha is an essential component of a transcription factor circuit whose role may be to maintain differentiated functions of pancreatic cells.
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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.