ArticleHepatology (Baltimore, Md.)2010
Integrated approach for the identification of human hepatocyte nuclear factor 4alpha target genes using protein binding microarrays.
Article in Hepatology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
124 citing papers in PubMed, 2 syntheses or guidelines pooled it, 170 citations in OpenAlex.
- Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits.Nature communications · 2025Pooled it
- Birth Cohort, Age, and Sex Strongly Modulate Effects of Lipid Risk Alleles Identified in Genome-Wide Association Studies.PloS one · 2015Pooled it
- HNF4α-HKDC1 axis orchestrates a metabolic rewiring to promote migration and metastasis in advanced gastric cancer.Cell death & disease · 2026Article
- Efimosfermin for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH): Mechanism of Action, Clinical Development and Emerging Therapeutic Potential.Drug design, development and therapy · 2026Review
- Multiscale characterization of an inflammatory macrophage state associated with an air pollutant-prioritized prognostic signature in gastric cancer.Frontiers in immunology · 2026Article
- Aip mutation leads to significant alterations in gene expression, altered sensitivity to Ahr ligands, and early lethality in zebrafish.Frontiers in toxicology · 2026Article
- 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
- Hnf4α integrates AIF and caspase 3/9 signaling to restrict single and coinfecting pathogens in teleosts.PLoS pathogens · 2025Article
- Deubiquitinase OTUD7B stabilizes HNF4α to alleviate pressure overload-induced cardiac hypertrophy by regulating fatty acid oxidation and inhibiting ferroptosis.Biomarker research · 2025Article
- Therapeutic Targets and Approaches to Manage Inflammation of NAFLD.Biomedicines · 2025Review
- HNF4α ubiquitination mediated by Peli1 impairs FAO and accelerates pressure overload-induced myocardial hypertrophy.Cell death & disease · 2024Article
- Hepatocyte Nuclear Factor 4α (HNF4α) Plays a Controlling Role in Expression of the Retinoic Acid Receptor β (International journal of molecular sciences · 2023Article
- HNF4α isoforms: the fraternal twin master regulators of liver function.Frontiers in endocrinology · 2023Review
- Structural insights into the HNF4 biology.Frontiers in endocrinology · 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
- SLU7: A New Hub of Gene Expression Regulation-From Epigenetics to Protein Stability in Health and Disease.International journal of molecular sciences · 2022Review
- Mitochondrial stress induces AREG expression and epigenomic remodeling through c-JUN and YAP-mediated enhancer activation.Nucleic acids research · 2022Article
- Spatial Environment Affects HNF4A Mutation-Specific Proteome Signatures and Cellular Morphology in hiPSC-Derived β-Like Cells.Diabetes · 2022Article
- Positive selection acts on regulatory genetic variants in populations of European ancestry that affect ALDH2 gene expression.Scientific reports · 2022Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 4 countries.
Funding
Abstract
unlabelledHepatocyte nuclear factor 4 alpha (HNF4alpha), a member of the nuclear receptor superfamily, is essential for liver function and is linked to several diseases including diabetes, hemophilia, atherosclerosis, and hepatitis. Although many DNA response elements and target genes have been identified for HNF4alpha, the complete repertoire of binding sites and target genes in the human genome is unknown. Here, we adapt protein binding microarrays (PBMs) to examine the DNA-binding characteristics of two HNF4alpha species (rat and human) and isoforms (HNF4alpha2 and HNF4alpha8) in a high-throughput fashion. We identified approximately 1400 new binding sequences and used this dataset to successfully train a Support Vector Machine (SVM) model that predicts an additional approximately 10,000 unique HNF4alpha-binding sequences; we also identify new rules for HNF4alpha DNA binding. We performed expression profiling of an HNF4alpha RNA interference knockdown in HepG2 cells and compared the results to a search of the promoters of all human genes with the PBM and SVM models, as well as published genome-wide location analysis. Using this integrated approach, we identified approximately 240 new direct HNF4alpha human target genes, including new functional categories of genes not typically associated with HNF4alpha, such as cell cycle, immune function, apoptosis, stress response, and other cancer-related genes.
conclusionWe report the first use of PBMs with a full-length liver-enriched transcription factor and greatly expand the repertoire of HNF4alpha-binding sequences and target genes, thereby identifying new functions for HNF4alpha. We also establish a web-based tool, HNF4 Motif Finder, that can be used to identify potential HNF4alpha-binding sites in any sequence.
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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.