Evidence map›Paper›PMID 22383578›Full record

ArticleNucleic acids research2012

Identification of a binding motif specific to HNF4 by comparative analysis of multiple nuclear receptors.

Bin Fang, Daniel Mane-Padros, Eugene Bolotin, Tao Jiang, Frances M Sladek

Abstract readComparative Study
In one paragraph

Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

74 citing papers in PubMed.

  1. The role of HNF4α in adenocarcinoma.Biochemical Society transactions · 2026
    Review
  2. Article
  3. Article
  4. Review
  5. Hepatocyte Nuclear Factor 4 Alpha: A Key Regulator of Liver Disease Pathology and Haemostatic Disorders.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Functional Analysis of a NovelJournal of the Endocrine Society · 2024
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Structural insights into the HNF4 biology.Frontiers in endocrinology · 2023
    Review

14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Bin FangDepartment of Cell Biology and Neuroscience, University of California Riverside, Riverside, CA 92521, USA.
Daniel Mane-Padros
Eugene Bolotin
Tao Jiang
Frances M Sladek

Funding

Nuclear Receptor DNA Binding in Human Physiology and DiseaseR01DK094707 · NIDDK · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI SLADEK, FRANCES M. · 2012 to 2015
$1.5M
Nuclear Receptor Networks in Human DiseaseR21MH087397 · NIMH · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI SLADEK, FRANCES M. · 2009 to 2010
$760k
NIDDK NIH HHS R01 DK094707NIMH NIH HHS MH087397NIMH NIH HHS R21 MH087397
6 · The paper itself

Abstract

Nuclear receptors (NRs) regulate gene expression by binding specific DNA sequences consisting of AG[G/T]TCA or AGAACA half site motifs in a variety of configurations. However, those motifs/configurations alone do not adequately explain the diversity of NR function in vivo. Here, a systematic examination of DNA binding specificity by protein-binding microarrays (PBMs) of three closely related human NRs--HNF4α, retinoid X receptor alpha (RXRα) and COUPTF2--reveals an HNF4-specific binding motif (H4-SBM), xxxxCAAAGTCCA, as well as a previously unrecognized polarity in the classical DR1 motif (AGGTCAxAGGTCA) for HNF4α, RXRα and COUPTF2 homodimers. ChIP-seq data indicate that the H4-SBM is uniquely bound by HNF4α but not 10 other NRs in vivo, while NRs PXR, FXRα, Rev-Erbα appear to bind adjacent to H4-SBMs. HNF4-specific DNA recognition and transactivation are mediated by residues Asp69 and Arg76 in the DNA-binding domain; this combination of amino acids is unique to HNF4 among all human NRs. Expression profiling and ChIP data predict ≈ 100 new human HNF4α target genes with an H4-SBM site, including several Co-enzyme A-related genes and genes with links to disease. These results provide important new insights into NR DNA binding.

Indexed as

Regulatory Elements, TranscriptionalArginineAspartic AcidBinding SitesCOUP Transcription Factor IIHepatocyte Nuclear Factor 4HumansNucleotide MotifsProtein Array AnalysisProtein BindingRetinoid X Receptor alphaTranscriptional ActivationArginineAspartic AcidCOUP Transcription Factor IIHepatocyte Nuclear Factor 4HNF4A protein, humanRetinoid X Receptor alpha

Identifiers

PMID22383578
PMCPMC3384313

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Registered trials

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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.