ArticleGene expression2010
Developmental and tissue-specific regulation of hepatocyte nuclear factor 4-alpha (HNF4-alpha) isoforms in rodents.
Article in Gene expression, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- A transcriptomic signature that predicts prehypertension in adolescence and higher systolic blood pressure in childhood.JCI insight · 2025Article
- The Wnt/β-catenin-P2-HNF4α feedback loop facilitates colorectal tumorigenesis and malignancy.Journal of translational medicine · 2025Article
- Hnf4α integrates AIF and caspase 3/9 signaling to restrict single and coinfecting pathogens in teleosts.PLoS pathogens · 2025Article
- Mechanism of paracrine communications between hepatic progenitor cells and endothelial cells.Cellular signalling · 2022Article
- Conserved roles for Hnf4 family transcription factors in zebrafish development and intestinal function.Genetics · 2022Article
- Hepatic circadian and differentiation factors control liver susceptibility for fatty liver disease and tumorigenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Prenatal glucocorticoid administration accelerates the maturation of fetal rat hepatocytes.Molecular biology reports · 2022Article
- [Culture of pluripotent stem cell-derived hepatocytes and organoids].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Article
- Transcription Control of Liver Development.Cells · 2021Review
- Hepatocyte nuclear factor 4α and cancer-related cell signaling pathways: a promising insight into cancer treatment.Experimental & molecular medicine · 2021Review
- Guide to the Assessment of Mature Liver Gene Expression in Stem Cell-Derived Hepatocytes.Stem cells and development · 2019Article
- 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
- Enhancer reprogramming in mammalian genomes.BMC bioinformatics · 2018Article
- Metformin attenuates angiotensin II-induced TGFβ1 expression by targeting hepatocyte nuclear factor-4-α.British journal of pharmacology · 2018Article
- Effects of Co-Culture Media on Hepatic Differentiation of hiPSC with or without HUVEC Co-Culture.International journal of molecular sciences · 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
- Synthetic Biology Platform for Sensing and Integrating Endogenous Transcriptional Inputs in Mammalian Cells.Cell reports · 2016Article
- Hepatocyte nuclear factor 4α is required for cell differentiation and homeostasis in the adult mouse gastric epithelium.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Opposing roles of nuclear receptor HNF4α isoforms in colitis and colitis-associated colon cancer.eLife · 2016Article
- Glucocorticoids accelerate maturation of the heme pathway in fetal liver through effects on transcription and DNA methylation.Epigenetics · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Hepatocyte nuclear factor 4-alpha (HNF4-alpha) regulates expression of a number of genes in several metabolic organs. The HNF4-alpha gene has two promoters and encodes at least nine isoforms through differential splicing. In mouse liver, transcription initiates at promoter 2 (P2) during fetal life, but switches to P1 at birth. Developmental and tissue-specific expression of HNF4-alpha in other organs is largely unknown. Here, we examined expression of P1- and P2-derived transcripts in a number of mouse and rat tissues. Both P1 and P2 were active in mouse fetal liver, but P2-derived isoforms were detected 50% more abundantly than P1 transcripts. Conversely, the adult mouse liver expressed significantly higher levels of P1- than P2-derived mRNA. In contrast, in the rat, P1 was used more predominantly in both fetal and adult liver. Exposure of fetal rats to the synthetic glucocorticoid dexamethasone caused suppression of P2 while enhancing hepatic expression of transcripts from P1. This was associated with increased expression of erythropoietin and phosphoenolpyruvate carboxykinase, which are key HNF4-alpha targets in the liver. Unlike liver, the kidney and stomach used promoters more selectively, so that only P1-derived isoforms were detected in fetal and adult kidneys in mice or rats, whereas the stomach in both species expressed P2-derived transcripts exclusively. No significant HNF4-alpha mRNA was detected in the spleen. These data reveal striking developmental and tissue-specific variation in expression of HNF4-alpha, and indicate that this can be influenced by environmental factors (such as exposure to glucocorticoid excess), with potential pathophysiological consequences.
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