ArticleMolecular and cellular biology2003
Association between hepatocyte nuclear factor 6 (HNF-6) and FoxA2 DNA binding domains stimulates FoxA2 transcriptional activity but inhibits HNF-6 DNA binding.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed, 75 citations in OpenAlex.
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- Article
- Article
- Novel Mechanisms for IGF-I Regulation by Glucagon in Carp Hepatocytes: Up-Regulation of HNF1α and CREB Expression via Signaling Crosstalk for IGF-I Gene Transcription.Frontiers in endocrinology · 2019Article
- Transcriptional regulation of metabolism in disease: From transcription factors to epigenetics.PeerJ · 2018Article
- HNF6 and Rev-erbα integrate hepatic lipid metabolism by overlapping and distinct transcriptional mechanisms.Genes & development · 2016Article
- Cross Talk Between GH-Regulated Transcription Factors HNF6 and CUX2 in Adult Mouse Liver.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Inhibition of hepatitis B virus gene expression and replication by hepatocyte nuclear factor 6.Journal of virology · 2015Article
- A Single Amino Acid in the Hinge Loop Region of the FOXP Forkhead Domain is Significant for Dimerisation.The protein journal · 2015Article
- Role of forkhead box protein A3 in age-associated metabolic decline.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Arx together with FoxA2, regulates Shh floor plate expression.Developmental biology · 2014Article
- Regulatory network rewiring for secondary metabolism in Arabidopsis thaliana under various conditions.BMC plant biology · 2014Article
- Hepatocyte nuclear factor 6 suppresses the migration and invasive growth of lung cancer cells through p53 and the inhibition of epithelial-mesenchymal transition.The Journal of biological chemistry · 2013Article
- Comprehensive identification of mutational cancer driver genes across 12 tumor types.Scientific reports · 2013Article
- The use of cellular technologies in treatment of liver pathologies.Acta naturae · 2012Article
- Forkhead box protein A2 (FOXA2) protein stability and activity are regulated by sumoylation.PloS one · 2012Article
- Stable expression of FoxA1 promotes pluripotent P19 embryonal carcinoma cells to be neural stem-like cells.Gene expression · 2012Article
- Inhibition of the liver enriched protein FOXA2 recovers HNF6 activity in human colon carcinoma and liver hepatoma cells.PloS one · 2010Article
- Stable chromatin binding prevents FoxA acetylation, preserving FoxA chromatin remodeling.The Journal of biological chemistry · 2010Article
- Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling.PLoS biology · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In previous studies we used transgenic mice or recombinant adenovirus infection to increase hepatic expression of forkhead box A2 (FoxA2, previously called hepatocyte nuclear factor 3beta [HNF-3beta]), which caused diminished hepatocyte glycogen levels and reduced expression of glucose homeostasis genes. Because this diminished expression of FoxA2 target genes was associated with reduced levels of the Cut-Homeodomain HNF-6 transcription factor, we conducted the present study to determine whether there is a functional interaction between HNF-6 and FoxA2. Human hepatoma (HepG2) cotransfection assays demonstrated that HNF-6 synergistically stimulated FoxA2 but not FoxA1 or FoxA3 transcriptional activity, and protein-binding assays showed that this protein interaction required the HNF-6 Cut-Homeodomain and FoxA2 winged-helix DNA binding domains. Furthermore, we show that the HNF-6 Cut-Homeodomain sequences were sufficient to synergistically stimulate FoxA2 transcriptional activation by recruiting the p300/CBP coactivator proteins. This was supported by the fact that FoxA2 transcriptional synergy with HNF-6 was dependent on retention of the HNF-6 Cut domain LXXLL sequence, which mediated recruitment of the p300/CBP proteins. Moreover, cotransfection and DNA binding assays demonstrated that increased FoxA2 levels caused a decrease in HNF-6 transcriptional activation of the glucose transporter 2 (Glut-2) promoter by interfering with the binding of HNF-6 to its target DNA sequence. These data suggest that at a FoxA-specific site, HNF-6 serves as a coactivator protein to enhance FoxA2 transcription, whereas at an HNF-6-specific site, FoxA2 represses HNF-6 transcription by inhibiting HNF-6 DNA binding activity. This is the first reported example of a liver-enriched transcription factor (HNF-6) functioning as a coactivator protein to potentiate the transcriptional activity of another liver factor, FoxA2.
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.