Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily.
Open accessAbstract
HNF-4 (hepatocyte nuclear factor 4) is a protein enriched in liver extracts that binds to sites required for the transcription of the genes for transthyretin (TTR), the carrier protein in the serum for vitamin A and thyroid hormone, and for apolipoprotein CIII (apoCIII), a major constituent of chylomicrons and very low-density lipoproteins (VLDL). Synthetic oligonucleotides derived from amino acid sequence of affinity-purified HNF-4 protein (54 kD) were used in the polymerase chain reaction (PCR) to isolate a cDNA clone encoding the protein. HNF-4 is a member of the steroid hormone receptor superfamily with an unusual amino acid in the conserved "knuckle" of the first zinc finger (DGCKG). Studies with in vitro-translated HNF-4 protein show that it binds to its recognition site as a dimer, and cotransfection assays indicate that it activates transcription in a sequence-specific fashion in nonhepatic (HeLa) cells. Northern blot analysis reveals that HNF-4 mRNA is present in kidney and intestine, as well as liver, but is absent in other tissues. DNA-binding and antisera reactivity data suggest that HNF-4 could be identical to liver factor A1 (LF-A1), a DNA-binding activity implicated in the regulation of transcription of the alpha 1-antitrypsin, apolipoprotein A1, and pyruvate kinase genes. The similarity between HNF-4 and other ligand-dependent transcription factors raises the possibility that HNF-4 and the genes it regulates respond to an as yet unidentified ligand.
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HNF4A controls genes that are crucial for liver functions, primarily through binding to enhancers.
“Hepatocyte nuclear factor 4A (HNF4A/NR2a1), a transcriptional regulator of hepatocyte identity, controls genes that are crucial for liver functions, primarily through binding to enhancers.”
From HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements (2024) · cites this paper as [1]
The Abstract and “HNF-4 and liver-specific gene expression” section describe HNF-4 binding to sites in, and helping regulate, genes with liver-related functions. But “Purification and characterization of HNF-4 protein” identifies key sites in the TTR and apoCIII promoters; the paper does not establish that HNF-4 acts primarily through enhancers. Page numbers were not available in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredHNF4A is expressed in the liver, pancreas, gastrointestinal tract and kidneys.
“Hepatocyte nuclear factor 4A (HNF4A, also known as NR2A1) is a member of the nuclear receptor superfamily of transcription factors (TFs) and is expressed in the liver, pancreas, gastrointestinal tract and kidneys (1).”
From Hepatocyte Nuclear Factor 4‐Alpha Is Essential for the Active Epigenetic State at Enhancers in Mouse Liver (2019) · cites this paper as [1]
The section “Tissue distribution of HNF-4 mRNA is limited” reports HNF-4 mRNA in rat liver, kidney, and intestine, supporting those parts of the claim. It does not report expression in the pancreas, and intestine is narrower than the gastrointestinal tract as a whole. (LLM, conf=0.89)
Experimental — accuracy not yet measured
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“Hepatocyte nuclear factor 4A (HNF4A; also known as NR2A1) is a member of the nuclear receptor superfamily of transcription factors (TFs) and is expressed in the liver, pancreas, gastrointestinal tract, and kidneys.(1) In liver, HNF4A is required for normal development,(2) including morphogenesis(3) and differentiation…”
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HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements
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- Authors
- Sladek, F. M., Zhong, W. M., Lai, E., & Darnell, J. E.
- Affiliations
- Rockefeller University (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1990-12-01
- Volume
- 4
- Issue
- 12b
- Pages
- 2353-2365
- ISSN
- 0890-9369 (ISSN-L)
- OpenAlex
- W2039307052
- Cited by
- 1,027
- References
- 3
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 12 · 2023: 22 · 2022: 10 · 2021: 21 · 2020: 12 · 2019: 19 · 2018: 10 · 2017: 16 · 2016: 15 · 2015: 22 · 2014: 26 · 2013: 21 · 2012: 22
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- National Institutes of Health
- 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 › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- HNF4, zinc finger transcription factor, prealbumin, apolipoprotein C-III, transcriptional activation, tissue-specific gene expression, ligand-dependent transcription factors, cDNA cloning
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Cell Nucleus, Cloning, Molecular, DNA-Binding Proteins, Multigene Family, Liver, Male, Molecular Sequence Data, Phosphoproteins, Rats, Inbred Strains, Receptors, Steroid, Recombinant Proteins, Sequence Homology, Nucleic Acid, Transcription Factors, Transcription, Genetic, Oligonucleotide Probes, Gene Expression, Macromolecular Substances, Rats, Hepatocyte Nuclear Factor 4
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