ArticleThe EMBO journal2006
In vivo role of the HNF4alpha AF-1 activation domain revealed by exon swapping.
Article in The EMBO journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed, 61 citations in OpenAlex.
- The role of HNF4α in adenocarcinoma.Biochemical Society transactions · 2026Review
- P2-HNF4α alters linoleic acid metabolism and mitigates soybean oil-induced obesity: role for oxylipins.Journal of lipid research · 2025Article
- Hepatocyte Nuclear Factor 4 Alpha: A Key Regulator of Liver Disease Pathology and Haemostatic Disorders.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- HNF4α in Hepatocyte Health and Disease.Seminars in liver disease · 2023Review
- HNF4α isoforms regulate the circadian balance between carbohydrate and lipid metabolism in the liver.Frontiers in endocrinology · 2023Article
- The protein architecture and allosteric landscape of HNF4α.Frontiers in endocrinology · 2023Review
- Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine.Frontiers in endocrinology · 2023Review
- HNF4α isoforms: the fraternal twin master regulators of liver function.Frontiers in endocrinology · 2023Review
- Therapeutic Potential of HNF4α in End-stage Liver Disease.Organogenesis · 2021Review
- Review
- HNF4A-AS1/hnRNPU/CTCF axis as a therapeutic target for aerobic glycolysis and neuroblastoma progression.Journal of hematology & oncology · 2020Article
- Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases.World journal of gastroenterology · 2019Review
- Type 2 Diabetes-Associated Genetic Polymorphisms as Potential Disease Predictors.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Review
- Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modulates tissue-specific circadian networks.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Incompatibility of the circadian protein BMAL1 and HNF4α in hepatocellular carcinoma.Nature communications · 2018Article
- Hepatocyte Nuclear Factor 4 Alpha Promotes Definitive Endoderm Differentiation from Human Induced Pluripotent Stem Cells.Stem cell reviews and reports · 2017Article
- Diabetes-linked transcription factor HNF4α regulates metabolism of endogenous methylarginines and β-aminoisobutyric acid by controlling expression of alanine-glyoxylate aminotransferase 2.Scientific reports · 2016Article
- Crosstalk of HNF4Acta pharmaceutica Sinica. B · 2016Review
- Opposing roles of nuclear receptor HNF4α isoforms in colitis and colitis-associated colon cancer.eLife · 2016Article
- Regulation of hepatocyte identity and quiescence.Cellular and molecular life sciences : CMLS · 2015Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The gene encoding the nuclear receptor hepatocyte nuclear factor 4alpha (HNF4alpha) generates isoforms HNF4alpha1 and HNF4alpha7 from usage of alternative promoters. In particular, HNF4alpha7 is expressed in the pancreas whereas HNF4alpha1 is found in liver, and mutations affecting HNF4alpha function cause impaired insulin secretion and/or hepatic defects in humans and in tissue-specific 'knockout' mice. HNF4alpha1 and alpha7 isoforms differ exclusively by amino acids encoded by the first exon which, in HNF4alpha1 but not in HNF4alpha7, includes the activating function (AF)-1 transactivation domain. To investigate the roles of HNF4alpha1 and HNF4alpha7 in vivo, we generated mice expressing only one isoform under control of both promoters, via reciprocal swapping of the isoform-specific first exons. Unlike Hnf4alpha gene disruption which causes embryonic lethality, these 'alpha7-only' and 'alpha1-only' mice are viable, indicating functional redundancy of the isoforms. However, the former show dyslipidemia and preliminary results indicate impaired glucose tolerance for the latter, revealing functional specificities of the isoforms. These 'knock-in' mice provide the first test in vivo of the HNF4alpha AF-1 function and have permitted identification of AF-1-dependent target genes.
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Registered trials
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.