Evidence map›Paper›PMID 22419066›Full record

ArticleEpigenetics2012

Selective DNA demethylation by fusion of TDG with a sequence-specific DNA-binding domain.

David J Gregory, Lyudmila Mikhaylova, Alexey V Fedulov

Open access · hybridAbstract read
In one paragraph

Article in Epigenetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.4field-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

17 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Role of Cadherins in Cancer-A Review.International journal of molecular sciences · 2020
    Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. New approaches to manipulating the epigenome.Dialogues in clinical neuroscience · 2014
    Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
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

3 authors at 1 institution in 1 country.

David J GregoryDepartment of Environmental Health, Harvard School of Public Health, Boston, MA, USA.
Lyudmila Mikhaylova
Alexey V Fedulov
Harvard University · US

Funding

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 K99/R00ES15425NIEHS NIH HHS R00 ES015425
6 · The paper itself

Abstract

Our ability to selectively manipulate gene expression by epigenetic means is limited, as there is no approach for targeted reactivation of epigenetically silenced genes, in contrast to what is available for selective gene silencing. We aimed to develop a tool for selective transcriptional activation by DNA demethylation. Here we present evidence that direct targeting of thymine-DNA-glycosylase (TDG) to specific sequences in the DNA can result in local DNA demethylation at potential regulatory sequences and lead to enhanced gene induction. When TDG was fused to a well-characterized DNA-binding domain [the Rel-homology domain (RHD) of NFκB], we observed decreased DNA methylation and increased transcriptional response to unrelated stimulus of inducible nitric oxide synthase (NOS2). The effect was not seen for control genes lacking either RHD-binding sites or high levels of methylation, nor in control mock-transduced cells. Specific reactivation of epigenetically silenced genes may thus be achievable by this approach, which provides a broadly useful strategy to further our exploration of biological mechanisms and to improve control over the epigenome.

Indexed as

DNA MethylationGene Expression Regulation, EnzymologicAnimalsBase SequenceBinding SitesCloning, MolecularCpG IslandsEnzyme InductionGene SilencingHumansInterferon-gammaMiceMice, Inbred C57BLNF-kappa BNitric Oxide Synthase Type IIPromoter Regions, GeneticInterferon-gammaNF-kappa BNitric Oxide Synthase Type IINOS2 protein, humanRecombinant Fusion ProteinsSTAT1 protein, humanSTAT1 Transcription FactorThymine DNA Glycosylase

Identifiers

PMID22419066
PMCPMC3368818
OpenAlexW2086575542

What OpenQuestion holds

Textmetadata
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.