ArticleThe Journal of biological chemistry2011
Proteomic analysis of native hepatocyte nuclear factor-4α (HNF4α) isoforms, phosphorylation status, and interactive cofactors.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT01771224 (Effect of Palmitoleic Acid), which is not on this map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
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.
Effect of Palmitoleic Acid (FAn-7) on Expression of HNF4γ and Ulcerative Colitis (UC) Activity
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Birth Cohort, Age, and Sex Strongly Modulate Effects of Lipid Risk Alleles Identified in Genome-Wide Association Studies.PloS one · 2015Pooled it
- Sex-specific KDM6A-HNF4A-CREBH network controls lipoprotein cholesterol metabolism and atherosclerosis via epigenetic reprograming of hepatocytes.Nature communications · 2026Article
- Epistatic contributions to human traits via transcription factor mechanisms.medRxiv : the preprint server for health sciences · 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
- A1AT dysregulation of metabolically stressed hepatocytes by Kupffer cells drives MASH and fibrosis.Experimental & molecular medicine · 2025Article
- Dynamic RNA polymerase II occupancy drives differentiation of the intestine under the direction of HNF4.Cell reports · 2024Article
- Dynamic RNA Polymerase II Recruitment Drives Differentiation of the Intestine under the direction of HNF4.bioRxiv : the preprint server for biology · 2023Article
- HNF4α isoforms: the fraternal twin master regulators of liver function.Frontiers in endocrinology · 2023Review
- Conserved roles for Hnf4 family transcription factors in zebrafish development and intestinal function.Genetics · 2022Article
- Mitochondrial stress induces AREG expression and epigenomic remodeling through c-JUN and YAP-mediated enhancer activation.Nucleic acids research · 2022Article
- Human transcription factor protein interaction networks.Nature communications · 2022Article
- Spatiotemporal dynamics of SETD5-containing NCoR-HDAC3 complex determines enhancer activation for adipogenesis.Nature communications · 2021Article
- Controversial roles of hepatocyte nuclear receptor 4 α on tumorigenesis.Oncology letters · 2021Review
- Synergistic regulation of hepatic Fsp27b expression by HNF4α and CREBH.Biochemical and biophysical research communications · 2020Article
- Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.Nature genetics · 2019Article
- Induction of Hepatic Metabolic Functions by a Novel Variant of Hepatocyte Nuclear Factor 4γ.Molecular and cellular biology · 2018Article
- Characteristics of the fads2 gene promoter in marine teleost Epinephelus coioides and role of Sp1-binding site in determining promoter activity.Scientific reports · 2018Article
- Aberrant Activation of a Gastrointestinal Transcriptional Circuit in Prostate Cancer Mediates Castration Resistance.Cancer cell · 2017Article
- Opposing roles of nuclear receptor HNF4α isoforms in colitis and colitis-associated colon cancer.eLife · 2016Article
- ROCK inhibition enhances microRNA function by promoting deadenylation of targeted mRNAs via increasing PAIP2 expression.Nucleic acids research · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocyte nuclear factor-4α (HNF4α, NR2A1) is a nuclear receptor that has a critical role in hepatocyte differentiation and the maintenance of homeostasis in the adult liver. However, a detailed understanding of native HNF4α in the steady-state remains to be elucidated. Here we report the native HNF4α isoform, phosphorylation status, and complexes in the steady-state, as shown by shotgun proteomics in HepG2 hepatocarcinoma cells. Shotgun proteomic analysis revealed the complexity of native HNF4α, including multiple phosphorylation sites and inter-isoform heterodimerization. The associating complexes identified by label-free semiquantitative proteomic analysis include the following: the DNA-dependent protein kinase catalytic subunit, histone acetyltransferase complexes, mRNA splicing complex, other nuclear receptor coactivator complexes, the chromatin remodeling complex, and the nucleosome remodeling and histone deacetylation complex. Among the associating proteins, GRB10 interacting GYF protein 2 (GIGYF2, PERQ2) is a new candidate cofactor in metabolic regulation. Moreover, an unexpected heterodimerization of HNF4α and hepatocyte nuclear factor-4γ was found. A biochemical and genomewide analysis of transcriptional regulation showed that this heterodimerization activates gene transcription. The genes thus transcribed include the cell death-inducing DEF45-like effector b (CIDEB) gene, which is an important regulator of lipid metabolism in the liver. This suggests that the analysis of the distinctive stoichiometric balance of native HNF4α and its cofactor complexes described here are important for an accurate understanding of transcriptional regulation.
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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.