ArticleMolecular and cellular biology2009
Hnf1alpha (MODY3) controls tissue-specific transcriptional programs and exerts opposed effects on cell growth in pancreatic islets and liver.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits.Nature communications · 2025Pooled it
- Defective HNF1A hinders GLI3 processing favoring duodenal versus pancreatic fate, thus leading to intestinal elongation in vivo.Genes & development · 2026Article
- Article
- The Genetic Landscape of Diabetes Mellitus: Lessons from Monogenic and Polygenic Forms.Life (Basel, Switzerland) · 2026Review
- Western Diet Induces Changes in Gene Expression in Multiple Tissues During Early Insulin Resistance and Glucose Intolerance in Male C57BL/6 Mice.Current issues in molecular biology · 2025Article
- Downregulation of hepatic sulfotransferase 1E1 expression associated with decreased expression of multidrug resistance-associated protein 2.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- 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
- Targeting FGFR4 abrogates HNF1A-driven metastasis in pancreatic ductal adenocarcinoma.Molecular cancer · 2025Article
- The age-dependent regulation of pancreatic islet landscape is fueled by a HNF1a-immune signaling loop.Mechanisms of ageing and development · 2024Article
- HNF4A and HNF1A exhibit tissue specific target gene regulation in pancreatic beta cells and hepatocytes.Nature communications · 2024Article
- Transcription regulation by long non-coding RNAs: mechanisms and disease relevance.Nature reviews. Molecular cell biology · 2024Review
- Integrating Mendelian randomization and single-cell RNA sequencing to identify therapeutic targets of baicalin for type 2 diabetes mellitus.Frontiers in pharmacology · 2024Article
- Article
- The role of noncoding RNAs in pancreatic birth defects.Birth defects research · 2023Review
- Dominant-negative HNF1α mutant promotes liver steatosis and inflammation by regulating hepatic complement factor D.iScience · 2023Article
- Human gain-of-function variants in HNF1A confer protection from diabetes but independently increase hepatic secretion of atherogenic lipoproteins.Cell genomics · 2023Article
- High-fat diet plus HNF1A variant promotes polyps by activating β-catenin in early-onset colorectal cancer.JCI insight · 2023Article
- HNF1A binds and regulates the expression of SLC51B to facilitate the uptake of estrone sulfate in human renal proximal tubule epithelial cells.Cell death & disease · 2023Article
- HNF1A regulates oxaliplatin resistance in pancreatic cancer by targeting 53BP1.International journal of oncology · 2023Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heterozygous HNF1A mutations cause pancreatic-islet beta-cell dysfunction and monogenic diabetes (MODY3). Hnf1alpha is known to regulate numerous hepatic genes, yet knowledge of its function in pancreatic islets is more limited. We now show that Hnf1a deficiency in mice leads to highly tissue-specific changes in the expression of genes involved in key functions of both islets and liver. To gain insights into the mechanisms of tissue-specific Hnf1alpha regulation, we integrated expression studies of Hnf1a-deficient mice with identification of direct Hnf1alpha targets. We demonstrate that Hnf1alpha can bind in a tissue-selective manner to genes that are expressed only in liver or islets. We also show that Hnf1alpha is essential only for the transcription of a minor fraction of its direct-target genes. Even among genes that were expressed in both liver and islets, the subset of targets showing functional dependence on Hnf1alpha was highly tissue specific. This was partly explained by the compensatory occupancy by the paralog Hnf1beta at selected genes in Hnf1a-deficient liver. In keeping with these findings, the biological consequences of Hnf1a deficiency were markedly different in islets and liver. Notably, Hnf1a deficiency led to impaired large-T-antigen-induced growth and oncogenesis in beta cells yet enhanced proliferation in hepatocytes. Collectively, these findings show that Hnf1alpha governs broad, highly tissue-specific genetic programs in pancreatic islets and liver and reveal key consequences of Hnf1a deficiency relevant to the pathophysiology of monogenic diabetes.
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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.