Hepatocyte Nuclear Factor 4 enhances the Hepatocyte Nuclear Factor 1 -mediated activation of transcription

Eeckhoute, J.

doi:10.1093/nar/gkh581

Cited by 71Genomics and Chromatin DynamicsLiver physiology and pathologyHepatocellular Carcinoma Treatment and Prognosis

Hepatocyte Nuclear Factor 4 enhances the Hepatocyte Nuclear Factor 1 -mediated activation of transcription

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Eeckhoute, J.·2004·Nucleic Acids Research

DOI 10.1093/nar/gkh581PMC PMC419469

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Abstract

Hepatocyte Nuclear Factor 1alpha (HNF1alpha) and Hepatocyte Nuclear Factor 4alpha (HNF4alpha) are two liver-enriched transcription factors coexpressed in specific tissues where they play a crucial role through their involvement in a complex cross-regulatory network. HNF1alpha down regulates HNF4alpha-mediated activation of transcription via a direct protein-protein interaction. Here we show that HNF4alpha enhances the transcriptional activity of HNF1alpha in a DNA binding independent manner, thus indicating that it behaves as a HNF1alpha coactivator. Using mutations in the ligand binding domain (LBD) of HNF4alpha, we confirmed the involvement of the Activation Function 2 module and demonstrated the requirement of the integrity of the LBD for the interaction with HNF1alpha. Moreover, we show that HNF4alpha cooperates with p300 to achieve the highest HNF1alpha-mediated transcription rates. Our findings highlight a new way by which HNF4alpha can regulate gene expression and extend our knowledge of the complexity of the transcriptional network involving HNF4alpha and HNF1alpha.

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HNF4A has been shown to interact with the histone acetyltransferase p300, although whether this is direct or through the MLL4 complex has not been confirmed.
“Moreover, HNF4A has been shown to interact with the histone acetyltransferase, p30062,63, although whether this is direct or through the MLL4 complex has not been confirmed.”
From HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements (2024) · cites this paper as [62]
HNF4A directly interacts with CBP/p300.
“HNF4A was shown to directly interact with CBP/p300, which may account for its ability to regulate H3K27ac (2, 41, 42).”
From Hepatocyte Nuclear Factor 4‐Alpha Is Essential for the Active Epigenetic State at Enhancers in Mouse Liver (2019) · cites this paper as [42]

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Hepatocyte Nuclear Factor 4a enhances the Hepatocyte Nuclear Factor 1a-mediated activation of
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Authors: Eeckhoute, J.
Affiliations: Inserm (FR)
Corresponding author: Eeckhoute, J.
ORCID: Eeckhoute, J.
Venue: Nucleic Acids Research
Publisher: Oxford University Press (OUP)
Published: 2004-04-28
Volume: 32
Issue: 8
Pages: 2586-2593
ISSN: 0305-1048 (ISSN-L)
1362-4962
DOI: 10.1093/nar/gkh581
PMC: PMC419469
OpenAlex: W2007722784
Cited by: 71
References: 43
Citations by year: 2026: 2 · 2025: 4 · 2024: 3 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 2 · 2018: 2 · 2017: 6 · 2016: 6 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 4
FWCI: 1.66
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Nucleic Acids Research (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
Keywords: HNF4α, HNF1A, transcriptional coactivator, transcriptional activation, protein-protein interaction, ligand-binding domain, AF-2, P300, liver-enriched transcription factors, transcriptional regulation, gene expression regulation
MeSH terms: DNA-Binding Proteins, HeLa Cells, Humans, Nuclear Proteins, Phosphoproteins, Transcription Factors, Transcriptional Activation, Trans-Activators, Protein Structure, Tertiary, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 4

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Hepatocyte Nuclear Factor 4 enhances the Hepatocyte Nuclear Factor 1 -mediated activation of transcription

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