Evidence map›Paper›PMID 30762521›Full record

ArticleeLife2019

Negative reciprocity, not ordered assembly, underlies the interaction of Sox2 and Oct4 on DNA.

John W Biddle, Maximilian Nguyen, Jeremy Gunawardena

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

20 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Emergence of activation or repression in transcriptional control under a fixed molecular context.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  7. Competing constraints shape the nonequilibrium limits of cellular decision-making.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
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  10. Pioneer Factor Improves CRISPR-Based C-To-G and C-To-T Base Editing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
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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

3 authors at 1 institution in 1 country.

John W BiddleDepartment of Systems Biology, Harvard Medical School, Boston, United States.
Maximilian NguyenDepartment of Systems Biology, Harvard Medical School, Boston, United States.
Jeremy GunawardenaDepartment of Systems Biology, Harvard Medical School, Boston, United States.ORCID 0000-0002-7280-1152
Harvard University · US

Funding

National Science Foundation 1462629
6 · The paper itself

Abstract

The mode of interaction of transcription factors (TFs) on eukaryotic genomes remains a matter of debate. Single-molecule data in living cells for the TFs Sox2 and Oct4 were previously interpreted as evidence of ordered assembly on DNA. However, the quantity that was calculated does not determine binding order but, rather, energy expenditure away from thermodynamic equilibrium. Here, we undertake a rigorous biophysical analysis which leads to the concept of reciprocity. The single-molecule data imply that Sox2 and Oct4 exhibit negative reciprocity, with expression of Sox2 increasing Oct4's genomic binding but expression of Oct4 decreasing Sox2's binding. Models show that negative reciprocity can arise either from energy expenditure or from a mixture of positive and negative cooperativity at distinct genomic loci. Both possibilities imply unexpected complexity in how TFs interact on DNA, for which single-molecule methods provide novel detection capabilities.

Indexed as

AnimalsBiophysical PhenomenaDNAGenetic LociGenetic VariationMarkov ChainsMiceModels, GeneticNIH 3T3 CellsOctamer Transcription Factor-3Protein BindingSOXB1 Transcription FactorsThermodynamicsDNAOctamer Transcription Factor-3SOXB1 Transcription Factorsgene regulationlinear frameworknonenon-equilibriumOct4 and Sox2physics of living systemssingle-molecule data

Identifiers

PMID30762521
PMCPMC6375704
OpenAlexW2915040067

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.