ArticleThe Journal of biological chemistry2008
Structural basis of natural promoter recognition by a unique nuclear receptor, HNF4alpha. Diabetes gene product.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 36 citations in OpenAlex.
- Molecular regulation of PGC-1α: from protein-protein interactions and post-translational modifications to pharmacological modulation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Mutational landscapes of HNF MODY gene products display a wide distribution with functional implications.Endocrine connections · 2025Review
- Why all MODY variants in transcription factor genes are dominantly inherited.Frontiers in genetics · 2025Article
- Functional characterization of HNF4A gene variants identify promoter and cell line specific transactivation effects.Human molecular genetics · 2024Article
- Structural insights into the HNF4 biology.Frontiers in endocrinology · 2023Review
- The protein architecture and allosteric landscape of HNF4α.Frontiers in endocrinology · 2023Review
- A Review of Functional Characterization of Single Amino Acid Change Mutations in HNF Transcription Factors in MODY Pathogenesis.The protein journal · 2021Review
- ErbB3-binding protein 1 (EBP1) represses HNF4α-mediated transcription and insulin secretion in pancreatic β-cells.The Journal of biological chemistry · 2019Article
- Loss-of-function mutations in Zn-finger DNA-binding domain ofOncotarget · 2018Article
- Transcriptional Regulation of CYP2D6 Expression.Drug metabolism and disposition: the biological fate of chemicals · 2017Review
- Preventing Gut Leakiness and Endotoxemia Contributes to the Protective Effect of Zinc on Alcohol-Induced Steatohepatitis in Rats.The Journal of nutrition · 2015Article
- TACO: a general-purpose tool for predicting cell-type-specific transcription factor dimers.BMC genomics · 2014Article
- Understanding nuclear receptor form and function using structural biology.Journal of molecular endocrinology · 2013Review
- Article
- Identification of a binding motif specific to HNF4 by comparative analysis of multiple nuclear receptors.Nucleic acids research · 2012Article
- MED25 is a mediator component of HNF4α-driven transcription leading to insulin secretion in pancreatic beta-cells.PloS one · 2012Article
- Aminopeptidases do not directly degrade tau protein.Molecular neurodegeneration · 2010Article
- The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase.Cell metabolism · 2010Article
- Integrated approach for the identification of human hepatocyte nuclear factor 4alpha target genes using protein binding microarrays.Hepatology (Baltimore, Md.) · 2010Article
- Multiple binding modes between HNF4alpha and the LXXLL motifs of PGC-1alpha lead to full activation.The Journal of biological chemistry · 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
7 authors at 1 institution in 1 country.
Funding
Abstract
HNF4alpha (hepatocyte nuclear factor 4alpha) plays an essential role in the development and function of vertebrate organs, including hepatocytes and pancreatic beta-cells by regulating expression of multiple genes involved in organ development, nutrient transport, and diverse metabolic pathways. As such, HNF4alpha is a culprit gene product for a monogenic and dominantly inherited form of diabetes, known as maturity onset diabetes of the young (MODY). As a unique member of the nuclear receptor superfamily, HNF4alpha recognizes target genes containing two hexanucleotide direct repeat DNA-response elements separated by one base pair (DR1) by exclusively forming a cooperative homodimer. We describe here the 2.0 angstroms crystal structure of human HNF4alpha DNA binding domain in complex with a high affinity promoter element of another MODY gene, HNF1alpha, which reveals the molecular basis of unique target gene selection/recognition, DNA binding cooperativity, and dysfunction caused by diabetes-causing mutations. The predicted effects of MODY mutations have been tested by a set of biochemical and functional studies, which show that, in contrast to other MODY gene products, the subtle disruption of HNF4alpha molecular function can cause significant effects in afflicted MODY patients.
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.