ArticleMolecular and cellular biology1999
Modulation of transcriptional activation and coactivator interaction by a splicing variation in the F domain of nuclear receptor hepatocyte nuclear factor 4alpha1.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 130 citations in OpenAlex.
- Stomach at the crossroads: nuclear receptor signaling at the interface between what we are and what we eat.Physiological reviews · 2026Review
- Mutational landscapes of HNF MODY gene products display a wide distribution with functional implications.Endocrine connections · 2025Review
- Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response.Communications biology · 2024Article
- HNF4α isoforms: the fraternal twin master regulators of liver function.Frontiers in endocrinology · 2023Review
- HNF4α isoforms regulate the circadian balance between carbohydrate and lipid metabolism in the liver.Frontiers in endocrinology · 2023Article
- Review
- Repression of hepatocyte nuclear factor 4 alpha by AP-1 underlies dyslipidemia associated with retinoic acid.Journal of lipid research · 2019Article
- Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modulates tissue-specific circadian networks.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Induction of Hepatic Metabolic Functions by a Novel Variant of Hepatocyte Nuclear Factor 4γ.Molecular and cellular biology · 2018Article
- Article
- Aberrant expression of alternative isoforms of transcription factors in hepatocellular carcinoma.World journal of hepatology · 2018Review
- Regulation of hepatocyte identity and quiescence.Cellular and molecular life sciences : CMLS · 2015Review
- Role of hepatocyte nuclear factor 4α (HNF4α) in cell proliferation and cancer.Gene expression · 2015Review
- Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases.Journal of experimental neuroscience · 2015Review
- Systematic dissection of coding exons at single nucleotide resolution supports an additional role in cell-specific transcriptional regulation.PLoS genetics · 2014Article
- Src tyrosine kinase phosphorylation of nuclear receptor HNF4α correlates with isoform-specific loss of HNF4α in human colon cancer.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- MED25 is a mediator component of HNF4α-driven transcription leading to insulin secretion in pancreatic beta-cells.PloS one · 2012Article
- General molecular biology and architecture of nuclear receptors.Current topics in medicinal chemistry · 2012Review
- What are nuclear receptor ligands?Molecular and cellular endocrinology · 2011Review
- Proteomic analysis of native hepatocyte nuclear factor-4α (HNF4α) isoforms, phosphorylation status, and interactive cofactors.The Journal of biological chemistry · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Transcription factors, such as nuclear receptors, often exist in various forms that are generated by highly conserved splicing events. Whereas the functional significance of these splicing variants is often not known, it is known that nuclear receptors activate transcription through interaction with coactivators. The parameters, other than ligands, that might modulate those interactions, however, are not well characterized, nor is the role of splicing variants. In this study, transient transfection, yeast two-hybrid, and GST pulldown assays are used to show not only that nuclear receptor hepatocyte nuclear factor 4 alpha1 (HNF4alpha1, NR2A1) interacts with GRIP1, and other coactivators, in the absence of ligand but also that the uncommonly large F domain in the C terminus of the receptor inhibits that interaction. In vitro, the F domain was found to obscure an AF-2-independent binding site for GRIP1 that did not map to nuclear receptor boxes II or III. The results also show that a natural splicing variant containing a 10-amino-acid insert in the middle of the F domain (HNF4alpha2) abrogates that inhibition in vivo and in vitro. A series of protease digestion assays indicates that there may be structural differences between HNF4alpha1 and HNF4alpha2 in the F domain as well as in the ligand binding domain (LBD). The data also suggest that there is a direct physical contact between the F domain and the LBD of HNF4alpha1 and -alpha2 and that that contact is different in the HNF4alpha1 and HNF4alpha2 isoforms. Finally, we propose a model in which the F domain of HNF4alpha1 acts as a negative regulatory region for transactivation and in which the alpha2 insert ameliorates the negative effect of the F domain. A conserved repressor sequence in the F domains of HNF4alpha1 and -alpha2 suggests that this model may be relevant to other nuclear receptors as well.
Indexed as
Identifiers
What OpenQuestion holds
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.