Evidence map›Paper›PMID 24008769›Full record

ArticleEpigenetics2013

Specific transcriptional enhancement of inducible nitric oxide synthase by targeted promoter demethylation.

David J Gregory, Yiming Zhang, Lester Kobzik, Alexey V Fedulov

Open access · bronzeAbstract read
In one paragraph

Article in Epigenetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

29 citing papers in PubMed, 44 citations in OpenAlex.

  1. Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026
    Review
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  8. TALENs-an indispensable tool in the era of CRISPR: a mini review.Journal, genetic engineering & biotechnology · 2021
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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

4 authors at 3 institutions in 1 country.

David J GregoryDepartment of Environmental Health; MIPS Program; Harvard School of Public Health; Boston, MA USA.
Yiming ZhangDepartment of Medicine; Division of Pulmonary and Critical Care Medicine; Brigham and Women's Hospital; Harvard Medical School; Boston, MA USA.
Lester KobzikDepartment of Environmental Health; MIPS Program; Harvard School of Public Health; Boston, MA USA.
Alexey V FedulovDepartment of Medicine; Division of Pulmonary and Critical Care Medicine; Brigham and Women's Hospital; Harvard Medical School; Boston, MA USA.
Pulmonary and Critical Care Associates · USHarvard University · USMassachusetts Department of Public Health · US

Funding

Translational Research Support CoreP30ES000002 · NIEHS · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI Gary Adamkiewicz · 1985 to 2026
$44.6M
Prenatal Programming of Neonatal Asthma SusceptibilityR01ES017588 · NIEHS · HARVARD SCHOOL OF PUBLIC HEALTH · PI KOBZIK, LESTER · 2009 to 2013
$2.5M
Inhaled environmental particles, pregnancy and neonatal allergyR00ES015425 · NIEHS · BRIGHAM AND WOMEN'S HOSPITAL · PI FEDULOV, ALEXEY V · 2010 to 2012
$747k
Inhaled environmental particles, pregnancy and neonatal allergyK99ES015425 · NIEHS · HARVARD SCHOOL OF PUBLIC HEALTH · PI FEDULOV, ALEXEY V · 2007 to 2008
$180k
NIEHS NIH HHS ES015425NIEHS NIH HHS ES017588NIEHS NIH HHS K99 ES015425NIEHS NIH HHS P30 ES000002NIEHS NIH HHS R00 ES015425NIEHS NIH HHS R01 ES017588
6 · The paper itself

Abstract

The ability to specifically reactivate epigenetically silenced genes would have great utility in experimental studies and potential therapeutic value. Here, we describe the specific targeting of thymidine DNA glycosylase (TDG), an enzyme involved in the mechanism of methylcytosine demethylation, to the promoter of Nos2, a gene silenced by methylation in fibroblasts, using artificial zinc finger DNA binding domains. Individual targeted TDG constructs had a small effect on Nos2 expression and methylation, but simultaneous targeting of a quartet of TDG constructs significantly restored responsiveness to LPS and IFN stimuli in association with marked cytosine demethylation at the promoter and CpG island; catalytically inactive TDG complexes had no effect. Whole-genome expression microarray and pathway analysis found only 42 genes that were affected by targeted TDG constructs; the majority are likely downstream of the effect on Nos2. This study therefore shows highly specific, directed reactivation of a single, silenced gene by targeting of a demethylase to the promoter.

Indexed as

DNA MethylationPromoter Regions, GeneticAnimalsCpG IslandsMiceNIH 3T3 CellsNitric Oxide Synthase Type IIThymine DNA GlycosylaseZinc FingersNitric Oxide Synthase Type IINos2 protein, mouseThymine DNA Glycosylasedemethylationepigenetic reactivationnitric oxide synthaseTDGzinc fingers

Identifiers

PMID24008769
PMCPMC5845820
OpenAlexW2000827155

What OpenQuestion holds

Textmetadata
LicenceTDM
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.