Evidence map›Paper›PMID 21706015›Full record

ArticleNature biotechnology2011

Direct measurement of DNA affinity landscapes on a high-throughput sequencing instrument.

Razvan Nutiu, Robin C Friedman, Shujun Luo, Irina Khrebtukova, David Silva, Robin Li, Lu Zhang, Gary P Schroth, Christopher B Burge

Abstract read
In one paragraph

Article in Nature biotechnology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed
–field-weighted citation impact
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

118 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Regulatory activity is the default DNA state in eukaryotes.Nature structural & molecular biology · 2024
    Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Physicochemical models of protein-DNA binding with standard and modified base pairs.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  15. Review
  16. Massively Parallel Selection of NanoCluster Beacons.Advanced materials (Deerfield Beach, Fla.) · 2022
    Article
  17. Article
  18. Article
  19. Review
  20. Review

58 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.

Razvan NutiuDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Robin C Friedman
Shujun Luo
Irina Khrebtukova
David Silva
Robin Li
Lu Zhang
Gary P Schroth
Christopher B Burge

Funding

Regulation and Function of Alternative mRNA Isoform Expression in MammalsR01HG002439 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BURGE, CHRISTOPHER B · 2002 to 2024
$9.7M
Identification and Function of Sequence-specific Splicing RegulatorsR01GM085319 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BURGE, CHRISTOPHER B · 2008 to 2025
$5.2M
NHGRI NIH HHS R01 HG002439NIGMS NIH HHS R01 GM085319
6 · The paper itself

Abstract

Several methods for characterizing DNA-protein interactions are available, but none have demonstrated both high throughput and quantitative measurement of affinity. Here we describe 'high-throughput sequencing'-'fluorescent ligand interaction profiling' (HiTS-FLIP), a technique for measuring quantitative protein-DNA binding affinity at unprecedented depth. In this approach, the optics built into a high-throughput sequencer are used to visualize in vitro binding of a protein to sequenced DNA in a flow cell. Application of HiTS-FLIP to the protein Gcn4 (Gcn4p), the master regulator of the yeast amino acid starvation response, yielded ~440 million binding measurements, enabling determination of dissociation constants for all 12-mer sequences having submicromolar affinity. These data revealed a complex interdependency between motif positions, allowed improved discrimination of in vivo Gcn4p binding sites and regulatory targets relative to previous methods and showed that sets of genes with different promoter affinities to Gcn4p have distinct functions and expression kinetics. Broad application of this approach should increase understanding of the interactions that drive transcription.

Indexed as

Chromatography, AffinityDNADNA-Binding ProteinsEquipment DesignEquipment Failure AnalysisProtein Interaction MappingSequence Analysis, DNASpectrometry, FluorescenceDNADNA-Binding Proteins

Identifiers

PMID21706015
PMCPMC3134637

What OpenQuestion holds

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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.