Evidence map›Paper›PMID 20176964›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2010

Specificity landscapes of DNA binding molecules elucidate biological function.

Clayton D Carlson, Christopher L Warren, Karl E Hauschild, Mary S Ozers, Naveeda Qadir, Devesh Bhimsaria, Youngsook Lee, Franco Cerrina, Aseem Z Ansari

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

65 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
  2. Article
  3. Defining the DNA Binding Specificity of GRHL2.bioRxiv : the preprint server for biology · 2026
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  5. Review
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  7. Article
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  9. Disease-associated non-coding variants alter NKX2-5 DNA-binding affinity.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023
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  11. Article
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  13. Article
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  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Specificity landscapes unmask submaximal binding site preferences of transcription factors.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article

5 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

9 authors at 2 institutions in 1 country.

Clayton D CarlsonDepartment of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
Christopher L Warren
Karl E Hauschild
Mary S Ozers
Naveeda Qadir
Devesh Bhimsaria
Youngsook Lee
Franco Cerrina
Aseem Z Ansari
University of Wisconsin–Madison · USEnergy Center of Wisconsin · US

Funding

Research Training for Computation and Informatics in Biology and MedicineT15LM007359 · NLM · UNIVERSITY OF WISCONSIN-MADISON · PI Mark W. Craven, Colin Noel Dewey · 2002 to 2026
$22.6M
Roles of transcription factors in cardiac developmentR01HL067050 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI LEE, YOUNGSOOK · 2002 to 2009
$2.7M
Targeting Leukemia causing oncogene E2a-Pbx1 with synthetic moleculesR01CA133508 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI ANSARI, ASEEM Z · 2008 to 2012
$1.5M
Modular design of synthetic transcriptional regulatorsR01GM069420 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI ANSARI, ASEEM Z · 2006 to 2010
$1.4M
NCI NIH HHS R01 CA133508NHLBI NIH HHS HL67050NHLBI NIH HHS R01 HL067050NIGMS NIH HHS GM069420NIGMS NIH HHS R01 GM069420NLM NIH HHS T15 LM007359NLM NIH HHS T15LM007359
6 · The paper itself

Abstract

Evaluating the specificity spectra of DNA binding molecules is a nontrivial challenge that hinders the ability to decipher gene regulatory networks or engineer molecules that act on genomes. Here we compare the DNA sequence specificities for different classes of proteins and engineered DNA binding molecules across the entire sequence space. These high-content data are visualized and interpreted using an interactive "specificity landscape" which simultaneously displays the affinity and specificity of a million-plus DNA sequences. Contrary to expectation, specificity landscapes reveal that synthetic DNA ligands match, and often surpass, the specificities of eukaryotic DNA binding proteins. The landscapes also identify differential specificity constraints imposed by diverse structural folds of natural and synthetic DNA binders. Importantly, the sequence context of a binding site significantly influences binding energetics, and utilizing the full contextual information permits greater accuracy in annotating regulatory elements within a given genome. Assigning such context-dependent binding values to every DNA sequence across the genome yields predictive genome-wide binding landscapes (genomescapes). A genomescape of a synthetic DNA binding molecule provided insight into its differential regulatory activity in cultured cells. The approach we describe will accelerate the creation of precision-tailored DNA therapeutics and uncover principles that govern sequence-specificity of DNA binding molecules.

Indexed as

AnimalsBase SequenceBinding SitesDNADNA-Binding ProteinsHomeobox Protein Nkx-2.5Homeodomain ProteinsMiceModels, MolecularNucleic Acid ConformationNylonsProtein BindingProtein FoldingProtein Structure, SecondaryTranscription FactorsDNADNA-Binding ProteinsHomeobox Protein Nkx-2.5Homeodomain ProteinsNkx2-5 protein, mouseNylonsTranscription Factors

Identifiers

PMID20176964
PMCPMC2842033
OpenAlexW2158042012

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.