Evidence map›Paper›PMID 25122745›Full record

ArticleNucleic acids research2014

Analysis of an artificial zinc finger epigenetic modulator: widespread binding but limited regulation.

Matthew R Grimmer, Sabine Stolzenburg, Ethan Ford, Ryan Lister, Pilar Blancafort, Peggy J Farnham

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

42 citing papers in PubMed, 67 citations in OpenAlex.

  1. Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025
    Review
  2. Review
  3. Review
  4. Article
  5. Neuroepigenetic Editing.Methods in molecular biology (Clifton, N.J.) · 2024
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Broadly active zinc finger protein-guided transcriptional activation of HIV-1.Molecular therapy. Methods & clinical development · 2021
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  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

6 authors at 4 institutions in 2 countries.

Matthew R GrimmerNorris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA Integrated Genetics and Genomics, University of California-Davis, Davis, CA 95616, USA.
Sabine StolzenburgDepartment of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA School of Anatomy, Physiology and Human Biology, M309, The University of Western Australia, Crawley, WA 6009, Australia.
Ethan FordAustralian Research Council Centre of Excellence in Plant Energy Biology, The University of Western Australia, Perth, WA 6009, Australia.
Ryan ListerAustralian Research Council Centre of Excellence in Plant Energy Biology, The University of Western Australia, Perth, WA 6009, Australia.
Pilar BlancafortDepartment of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA School of Anatomy, Physiology and Human Biology, M309, The University of Western Australia, Crawley, WA 6009, Australia Cancer Epigenetics Group, Harry Perkins Institute of Medical Research, Nedlands, WA 6008, Australia pfarnham@usc.edu.
Peggy J FarnhamNorris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA pfarnham@usc.edu.
University of North Carolina at Chapel Hill · USUniversity of Western Australia · AUSequenom (United States) · USUniversity of Southern California · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
Targeted epigenetic silencing of oncogenic Transcription Factors (PQ18)R01CA170370 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BLANCAFORT, PILAR · 2012 to 2015
$900k
Development of a nuclease-mediated technology to validate chromatin hubsR21HG006761 · NHGRI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI FARNHAM, PEGGY J · 2012 to 2013
$476k
Precision engineering of DNA methylation patterns in the human genomeR01DA036906 · NIDA · UNIVERSITY OF WESTERN AUSTRALIA · PI BLANCAFORT, PILAR, LISTER, RYAN · 2013 to 2014
$350k
NCI NIH HHS P30CA014089NCI NIH HHS R01 CA170370NCI NIH HHS R01CA170370NHGRI NIH HHS R21HG006761NIDA NIH HHS R01DA036906
6 · The paper itself

Abstract

Artificial transcription factors (ATFs) and genomic nucleases based on a DNA binding platform consisting of multiple zinc finger domains are currently being developed for clinical applications. However, no genome-wide investigations into their binding specificity have been performed. We have created six-finger ATFs to target two different 18 nt regions of the human SOX2 promoter; each ATF is constructed such that it contains or lacks a super KRAB domain (SKD) that interacts with a complex containing repressive histone methyltransferases. ChIP-seq analysis of the effector-free ATFs in MCF7 breast cancer cells identified thousands of binding sites, mostly in promoter regions; the addition of an SKD domain increased the number of binding sites ∼ 5-fold, with a majority of the new sites located outside of promoters. De novo motif analyses suggest that the lack of binding specificity is due to subsets of the finger domains being used for genomic interactions. Although the ATFs display widespread binding, few genes showed expression differences; genes repressed by the ATF-SKD have stronger binding sites and are more enriched for a 12 nt motif. Interestingly, epigenetic analyses indicate that the transcriptional repression caused by the ATF-SKD is not due to changes in active histone modifications.

Indexed as

Epigenesis, GeneticZinc FingersBinding SitesDNA-Binding ProteinsGenome, HumanHumansMCF-7 CellsPromoter Regions, GeneticProtein BindingTranscription FactorsDNA-Binding ProteinsTranscription Factors

Identifiers

PMID25122745
PMCPMC4176344
OpenAlexW2011235782

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.