ArticleHepatology (Baltimore, Md.)2019
Hepatocyte Nuclear Factor 4-Alpha Is Essential for the Active Epigenetic State at Enhancers in Mouse Liver.
Article in Hepatology (Baltimore, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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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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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
42 citing papers in PubMed, 70 citations in OpenAlex.
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- Genetic or pharmacological inhibition of hepatic TMEM141 attenuates MASH and fibrosis via the ROS-HNF4α signaling pathway.Nature communications · 2026Article
- FOXM1 inhibition primes terminal differentiation of human iPSC-derived hepatocytes.Cell death discovery · 2026Article
- Constitutive AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity.Science advances · 2026Article
- Review
- Inhibition of the U12-type splicing factor ZCRB1 mediates retention of the USP21 minor intron to suppress malignant progression in hepatocellular carcinoma.Hepatology international · 2026Article
- Genetic variation shapes the chromatin accessibility landscape and transcriptional responses in mouse adipose tissue.PLoS genetics · 2026Article
- Review
- Hepatocyte nuclear factor 4-Alpha: a key regulator in liver carcinogenesis.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Article
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response.Communications biology · 2024Article
- Wnt/β-catenin signaling pathway in liver biology and tumorigenesis.In vitro cellular & developmental biology. Animal · 2024Review
- HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements.Communications biology · 2024Article
- Transcriptional Control: A Directional Sign at the Crossroads of Adult Hepatic Progenitor Cells' Fates.International journal of biological sciences · 2024Review
- Establishment of a Fah-LSL mouse model to study BEC-to-hepatocyte conversion.Biophysics reports · 2023Article
- Fetal liver development and implications for liver disease pathogenesis.Nature reviews. Gastroenterology & hepatology · 2023Review
- TET (Ten-eleven translocation) family proteins: structure, biological functions and applications.Signal transduction and targeted therapy · 2023Review
- FXR Friend-ChIPs in the Enterohepatic System.Seminars in liver disease · 2023Review
- TET2 and TET3 loss disrupts small intestine differentiation and homeostasis.Nature communications · 2023Article
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 4 countries.
Funding
Abstract
Cell-fate determination is influenced by interactions between master transcription factors (TFs) and cis-regulatory elements. Hepatocyte nuclear factor 4 alpha (HNF4A), a liver-enriched TF, acts as a master controller in specification of hepatic progenitor cells by regulating a network of TFs to control onset of hepatocyte cell fate. Using analysis of genome-wide histone modifications, DNA methylation, and hydroxymethylation in mouse hepatocytes, we show that HNF4A occupies active enhancers in hepatocytes and is essential for active histone and DNA signatures, especially acetylation of lysine 27 of histone 3 (H3K27ac) and 5-hydroxymethylcytosine (5hmC). In mice lacking HNF4A protein in hepatocytes, we observed a decrease in both H3K27ac and hydroxymethylation at regions bound by HNF4A. Mechanistically, HNF4A-associated hydroxymethylation (5hmC) requires its interaction with ten-eleven translocation methylcytosine dioxygenase 3 (TET3), a protein responsible for oxidation from 5mC to 5hmC. Furthermore, HNF4A regulates TET3 expression in liver by directly binding to an enhancer region. Conclusion: In conclusion, we identified that HNF4A is required for the active epigenetic state at enhancers that amplifies transcription of genes in hepatocytes.
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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.