Evidence map›Paper›PMID 14514889›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2003

Zinc-finger protein-targeted gene regulation: genomewide single-gene specificity.

Siyuan Tan, Dmitry Guschin, Albert Davalos, Ya-Li Lee, Andrew W Snowden, Yann Jouvenot, H Steven Zhang, Katherine Howes, Andrew R McNamara, Albert Lai and 12 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

61 citing papers in PubMed, 151 citations in OpenAlex.

  1. Controlling gene expression through five zinc finger domains of ZNF18.Protein science : a publication of the Protein Society · 2025
    Article
  2. Review
  3. Neuroepigenetic Editing.Methods in molecular biology (Clifton, N.J.) · 2024
    Review
  4. Article
  5. Article
  6. Delivery of transcription factors as modulators of cell differentiation.Drug delivery and translational research · 2021
    Review
  7. Article
  8. Functional characterization of SOX2 as an anticancer target.Signal transduction and targeted therapy · 2020
    Review
  9. Article
  10. The past and presence of gene targeting: from chemicals and DNA via proteins to RNA.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018
    Review
  11. Neuroepigenetic Editing.Methods in molecular biology (Clifton, N.J.) · 2018
    Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article

1 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

22 authors at 4 institutions in 2 countries.

Siyuan TanSangamo BioSciences, Inc., Point Richmond Tech Center II, 501 Canal Boulevard, Richmond, CA 94804, USA.
Dmitry Guschin
Albert Davalos
Ya-Li Lee
Andrew W Snowden
Yann Jouvenot
H Steven Zhang
Katherine Howes
Andrew R McNamara
Albert Lai
Chris Ullman
Lindsey Reynolds
Michael Moore
Mark Isalan
Lutz-Peter Berg
Bradley Campos
Hong Qi
S Kaye Spratt
Casey C Case
Carl O Pabo
Judith Campisi
Philip D Gregory
European Molecular Biology Laboratory · DEPoint Richmond Tech Center · USSangamo BioSciences (United States) · USLawrence Berkeley National Laboratory · US

Funding

Training in Basic Research on Aging and Age-Related DiseaseT32AG000266 · NIA · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Lisa M Ellerby · 1998 to 2026
$13.8M
Senescence and Longevity Modulating Genes, WRN and BLMR01AG011658 · NIA · UNIVERSITY OF CALIFORNIA BERKELEY · PI CAMPISI, JUDITH · 1993 to 2008
$2.7M
Targeted VEGF Methylation: Novel Cancer TherapyR44CA094795 · NCI · SANGAMO BIOSCIENCES, INC. · PI GREGORY, PHILIP D · 2002 to 2003
$476k
NCI NIH HHS 9R44 CA 94795-02NIA NIH HHS AG 00266NIA NIH HHS AG 11658NIA NIH HHS R01 AG011658NIA NIH HHS T32 AG000266
6 · The paper itself

Abstract

Zinc-finger protein transcription factors (ZFP TFs) can be designed to control the expression of any desired target gene, and thus provide potential therapeutic tools for the study and treatment of disease. Here we report that a ZFP TF can repress target gene expression with single-gene specificity within the human genome. A ZFP TF repressor that binds an 18-bp recognition sequence within the promoter of the endogenous CHK2 gene gives a >10-fold reduction in CHK2 mRNA and protein. This level of repression was sufficient to generate a functional phenotype, as demonstrated by the loss of DNA damage-induced CHK2-dependent p53 phosphorylation. We determined the specificity of repression by using DNA microarrays and found that the ZFP TF repressed a single gene (CHK2) within the monitored genome in two different cell types. These data demonstrate the utility of ZFP TFs as precise tools for target validation, and highlight their potential as clinical therapeutics.

Indexed as

Gene Expression RegulationProtein Serine-Threonine KinasesBase SequenceBinding SitesCell LineCheckpoint Kinase 2DNADNA DamageGene Expression Regulation, EnzymologicGenome, HumanHumansPromoter Regions, GeneticProtein EngineeringProtein KinasesRecombinant ProteinsRepressor ProteinsCheckpoint Kinase 2CHEK2 protein, humanDNAProtein KinasesProtein Serine-Threonine KinasesRecombinant ProteinsRepressor ProteinsRNA, MessengerTranscription Factors

Identifiers

PMID14514889
PMCPMC218702
OpenAlexW2171050607

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.