Evidence map›Paper›PMID 25762553›Full record

ArticleGenome research2015

Unraveling determinants of transcription factor binding outside the core binding site.

Michal Levo, Einat Zalckvar, Eilon Sharon, Ana Carolina Dantas Machado, Yael Kalma, Maya Lotam-Pompan, Adina Weinberger, Zohar Yakhini, Remo Rohs, Eran Segal

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Genome research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 100 papers.

0numbers the graph read from it
0cells of the map it votes in
100citing 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

100 citing papers in PubMed, 165 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. TF paralogs-Natural experiments in DNA binding.Current opinion in structural biology · 2025
    Review
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  8. Review
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  12. Review
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  15. Review
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  17. Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  18. Article
  19. Article
  20. Article

40 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Michal LevoDepartment of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel;
Einat ZalckvarDepartment of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel;
Eilon SharonDepartment of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel;
Ana Carolina Dantas MachadoMolecular and Computational Biology Program, Departments of Biological Sciences, Chemistry, Physics, and Computer Science, University of Southern California, Los Angeles, California 90089, USA;
Yael KalmaDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel;
Maya Lotam-PompanDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel;
Adina WeinbergerDepartment of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel;
Zohar YakhiniComputer Science Department, Technion-Israel Institute of Technology, Haifa 32000, Israel; Agilent Laboratories, Santa Clara, California 95051, USA.
Remo RohsMolecular and Computational Biology Program, Departments of Biological Sciences, Chemistry, Physics, and Computer Science, University of Southern California, Los Angeles, California 90089, USA;
Eran SegalDepartment of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel;
Weizmann Institute of Science · ILUniversity of Southern California · USTechnion – Israel Institute of Technology · IL

Funding

Multi-scale modeling of genetic variation in a developmental networkU01GM103804 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DEPACE, ANGELA H, MARJORAM, PAUL · 2013 to 2016
$2.0M
Genome analysis based on the integration of DNA sequence and shapeR01GM106056 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROHS, REMO · 2014 to 2017
$1.3M
NIGMS NIH HHS R01 GM106056NIGMS NIH HHS R01GM106056NIGMS NIH HHS U01 GM103804NIGMS NIH HHS U01GM103804
6 · The paper itself

Abstract

Binding of transcription factors (TFs) to regulatory sequences is a pivotal step in the control of gene expression. Despite many advances in the characterization of sequence motifs recognized by TFs, our ability to quantitatively predict TF binding to different regulatory sequences is still limited. Here, we present a novel experimental assay termed BunDLE-seq that provides quantitative measurements of TF binding to thousands of fully designed sequences of 200 bp in length within a single experiment. Applying this binding assay to two yeast TFs, we demonstrate that sequences outside the core TF binding site profoundly affect TF binding. We show that TF-specific models based on the sequence or DNA shape of the regions flanking the core binding site are highly predictive of the measured differential TF binding. We further characterize the dependence of TF binding, accounting for measurements of single and co-occurring binding events, on the number and location of binding sites and on the TF concentration. Finally, by coupling our in vitro TF binding measurements, and another application of our method probing nucleosome formation, to in vivo expression measurements carried out with the same template sequences serving as promoters, we offer insights into mechanisms that may determine the different expression outcomes observed. Our assay thus paves the way to a more comprehensive understanding of TF binding to regulatory sequences and allows the characterization of TF binding determinants within and outside of core binding sites.

Indexed as

Binding SitesComputational BiologyNucleosomesPoly APoly TProtein BindingRegulatory Sequences, Nucleic AcidSaccharomyces cerevisiaeThermodynamicsTranscription FactorsNucleosomesPoly Apoly(dA)Poly TTranscription Factors

Identifiers

PMID25762553
PMCPMC4484385
OpenAlexW2122429294

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.