Evidence map›Paper›PMID 23408851›Full record

ArticleNucleic acids research2013

Quantitative analysis of TALE-DNA interactions suggests polarity effects.

Joshua F Meckler, Mital S Bhakta, Moon-Soo Kim, Robert Ovadia, Chris H Habrian, Artem Zykovich, Abigail Yu, Sarah H Lockwood, Robert Morbitzer, Janett Elsäesser and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
15.5field-weighted citation impact, top 1% 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

86 citing papers in PubMed, 155 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Tuning up Transcription Factors for Therapy.Molecules (Basel, Switzerland) · 2020
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Selective recognition ofPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018
    Article
  17. Review
  18. Article
  19. Article
  20. Article

26 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

13 authors at 2 institutions in 2 countries.

Joshua F MecklerGenome Center and Department of Biochemistry and Molecular Medicine, University of California, Davis, CA 95616, USA.
Mital S Bhakta
Moon-Soo Kim
Robert Ovadia
Chris H Habrian
Artem Zykovich
Abigail Yu
Sarah H Lockwood
Robert Morbitzer
Janett Elsäesser
Thomas Lahaye
David J Segal
Enoch P Baldwin
University of California, Davis · USLudwig-Maximilians-Universität München · DE

Funding

Training Program In Basic & Translational Cardiovascular ScienceT32HL086350 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Martin Cadeiras, David A. Liem · 2008 to 2026
$7.1M
NextGen DNA Binding Proteins Based on TAL DomainsR01GM097073 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SEGAL, DAVID J · 2011 to 2014
$1.1M
NHLBI NIH HHS T32 HL086350NIGMS NIH HHS GM097073
6 · The paper itself

Abstract

Transcription activator-like effectors (TALEs) have revolutionized the field of genome engineering. We present here a systematic assessment of TALE DNA recognition, using quantitative electrophoretic mobility shift assays and reporter gene activation assays. Within TALE proteins, tandem 34-amino acid repeats recognize one base pair each and direct sequence-specific DNA binding through repeat variable di-residues (RVDs). We found that RVD choice can affect affinity by four orders of magnitude, with the relative RVD contribution in the order NG > HD ≈ NN >> NI > NK. The NN repeat preferred the base G over A, whereas the NK repeat bound G with 10(3)-fold lower affinity. We compared AvrBs3, a naturally occurring TALE that recognizes its target using some atypical RVD-base combinations, with a designed TALE that precisely matches 'standard' RVDs with the target bases. This comparison revealed unexpected differences in sensitivity to substitutions of the invariant 5'-T. Another surprising observation was that base mismatches at the 5' end of the target site had more disruptive effects on affinity than those at the 3' end, particularly in designed TALEs. These results provide evidence that TALE-DNA recognition exhibits a hitherto un-described polarity effect, in which the N-terminal repeats contribute more to affinity than C-terminal ones.

Indexed as

DNADNA-Binding ProteinsProtein BindingRepetitive Sequences, Amino AcidTrans-ActivatorsTranscriptional ActivationDNADNA-Binding ProteinsTrans-Activators

Identifiers

PMID23408851
PMCPMC3627578
OpenAlexW2121138707

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.