Evidence map›Paper›PMID 22583700›Full record

ArticleFree radical biology & medicine2012

Promoter G-quadruplex sequences are targets for base oxidation and strand cleavage during hypoxia-induced transcription.

David W Clark, Tzu Phang, Michael G Edwards, Mark W Geraci, Mark N Gillespie

Open access · greenAbstract read
In one paragraph

Article in Free radical biology & medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
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

53 citing papers in PubMed, 79 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?International journal of molecular sciences · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. DNA G-Quadruplex Is a Transcriptional Control Device That Regulates Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  11. Article
  12. Article
  13. PromotersRSC chemical biology · 2023
    Article
  14. Review
  15. The Intertwined Role of 8-oxodG and G4 in Transcription Regulation.International journal of molecular sciences · 2023
    Review
  16. Crosstalk between G-quadruplex and ROS.Cell death & disease · 2023
    Review
  17. Review
  18. Review
  19. Integration of DNA Repair, Antigenic Variation, Cytoadhesion, and Chance inFrontiers in cellular and infection microbiology · 2022
    Article
  20. Article
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 at 2 institutions in 1 country.

David W ClarkDepartment of Pharmacology and Center for Lung Biology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA.
Tzu Phang
Michael G Edwards
Mark W Geraci
Mark N Gillespie
University of Colorado Denver · USUniversity of South Alabama · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR025780 · NCRR · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2008 to 2011
$61.3M
DNA LESIONS AND GENE EXPRESSION IN HYPOXIC LUNG DISEASER01HL058234 · NHLBI · UNIVERSITY OF SOUTH ALABAMA · PI GILLESPIE, MARK N · 1998 to 2018
$5.2M
Lung Cell Genomic Threats from Physiological SignalsR01HL073244 · NHLBI · UNIVERSITY OF SOUTH ALABAMA · PI GILLESPIE, MARK N · 2005 to 2009
$1.8M
NCI NIH HHS P30 CA046934NCRR NIH HHS UL1 RR025780NHLBI NIH HHS HL073244NHLBI NIH HHS R01 HL058234NHLBI NIH HHS R01 HL073244NHLBI NIH HHS R01 HL58234
6 · The paper itself

Abstract

The G-quadruplex, a non-B DNA motif that forms in certain G-rich sequences, is often located near transcription start sites in growth regulatory genes. Multiple lines of evidence show that reactive oxygen species generated as second messengers during physiologic signaling target specific DNA sequences for oxidative base modifications. Because guanine repeats are uniquely sensitive to oxidative damage, and G4 sequences are known "hot spots" for genetic mutation and DNA translocation, we hypothesized that G4 sequences are targeted for oxidative base modifications in hypoxic signaling. Approximately 25% of hypoxia-regulated genes in pulmonary artery endothelial cells harbored G4 sequences within their promoters. Chromatin immunoprecipitation showed that common base oxidation product 8-oxoguanine was selectively introduced into G4s, in promoters of hypoxia up-, down-, and nonregulated genes. Additionally, base excision DNA repair (BER) enzymes were recruited, and transient strand breaks formed in these sequences. Transcription factor Sp1, constitutively bound to G4 sequences in normoxia, was evicted as 8-oxoguanine accumulated during hypoxic exposure. Blocking hypoxia-induced oxidant production prevented both base modifications and decreased Sp1 binding. These findings suggest that oxidant stress in hypoxia causes oxidative base modifications, recruitment of BER enzymes, and transient strand breaks in G4 promoter sequences potentially altering G4 integrity and function.

Indexed as

G-QuadruplexesHypoxiaTranscription, GeneticAnimalsBiomarkersCells, CulturedChromatin ImmunoprecipitationDNADNA RepairEndothelium, VascularGene Expression ProfilingGuanineOligonucleotide Array Sequence AnalysisOxidation-ReductionOxidative StressPromoter Regions, GeneticBiomarkersDNAGuanineReactive Oxygen Species

Identifiers

PMID22583700
PMCPMC3377816
OpenAlexW2002675613

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.