Evidence map›Paper›PMID 34354236›Full record

ArticleNature cell biology2021

Dissecting OCT4 defines the role of nucleosome binding in pluripotency.

Gareth A Roberts, Burak Ozkan, Ivana Gachulincová, Michael R O'Dwyer, Elisa Hall-Ponsele, Manoj Saxena, Philip J Robinson, Abdenour Soufi

Open access · greenAbstract read
In one paragraph

Article in Nature cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.9field-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

48 citing papers in PubMed, 60 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Cohesin Facilitates Nucleosome Invasion by Transcription Factors.bioRxiv : the preprint server for biology · 2025
    Article
  8. Circadian regulator REV-ERBα is a master regulator of tumor lineage plasticity and an effective therapeutic target.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Cell reprogramming: methods, mechanisms and applications.Cell regeneration (London, England) · 2025
    Review
  14. Article
  15. Article
  16. HIRA and dPCIF1 coordinately establish totipotent chromatin and control orderly ZGA inProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  17. Article
  18. Article
  19. Review
  20. Review
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

8 authors at 2 institutions in 1 country.

Gareth A Roberts *Centre for Regenerative Medicine, Institute for Regeneration and Repair, Institute of Stem Cell Research, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-3726-390X
Burak Ozkan *Centre for Regenerative Medicine, Institute for Regeneration and Repair, Institute of Stem Cell Research, University of Edinburgh, Edinburgh, UK.
Ivana GachulincováCentre for Regenerative Medicine, Institute for Regeneration and Repair, Institute of Stem Cell Research, University of Edinburgh, Edinburgh, UK.
Michael R O'DwyerCentre for Regenerative Medicine, Institute for Regeneration and Repair, Institute of Stem Cell Research, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-1371-1421
Elisa Hall-PonseleCentre for Regenerative Medicine, Institute for Regeneration and Repair, Institute of Stem Cell Research, University of Edinburgh, Edinburgh, UK.
Manoj SaxenaInstitute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, London, UK.ORCID http://orcid.org/0000-0002-0281-4222
Philip J RobinsonInstitute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, London, UK.
Abdenour SoufiCentre for Regenerative Medicine, Institute for Regeneration and Repair, Institute of Stem Cell Research, University of Edinburgh, Edinburgh, UK. Abdenour.Soufi@ed.ac.uk.ORCID http://orcid.org/0000-0002-3666-3266
MRC Centre for Regenerative Medicine · GBInstitute of Structural and Molecular Biology · GB

Funding

Biotechnology and Biological Sciences Research Council BB/M010996/1Biotechnology and Biological Sciences Research Council BB/M0180404/1Cancer Research UK 26986Cancer Research UK C65925/A26986Medical Research Council MR/N024028/1Medical Research Council MR/R008795/1Wellcome Trust
6 · The paper itself

Abstract

Pioneer transcription factors such as OCT4 can target silent genes embedded in nucleosome-dense regions. How nucleosome interaction enables transcription factors to target chromatin and determine cell identity remains elusive. Here, we systematically dissect OCT4 to show that nucleosome binding is encoded within the DNA-binding domain and yet can be uncoupled from free-DNA binding. Furthermore, accelerating the binding kinetics of OCT4 to DNA enhances nucleosome binding. In cells, uncoupling nucleosome binding diminishes the ability of OCT4 to individually access closed chromatin, while more dynamic nucleosome binding results in expansive genome scanning within closed chromatin. However, both uncoupling and enhancing nucleosome binding are detrimental to inducing pluripotency from differentiated cells. Remarkably, stable interactions between OCT4 and nucleosomes are continuously required for maintaining the accessibility of pluripotency enhancers in stem cells. Our findings reveal how the affinity and residence time of OCT4-nucleosome complexes modulate chromatin accessibility during cell fate changes and maintenance.

Indexed as

AnimalsBinding SitesChromatinEnhancer Elements, GeneticFemaleFibroblastsGene LibraryHumansMiceModels, MolecularMutationNucleosomesOctamer Transcription Factor-3Pluripotent Stem CellsProtein BindingSOXB1 Transcription FactorsChromatinNucleosomesOctamer Transcription Factor-3POU5F1 protein, humanSOX2 protein, humanSOXB1 Transcription Factors

Identifiers

PMID34354236
PMCPMC7611526
OpenAlexW3189091039

What OpenQuestion holds

Textmetadata
LicenceTDM
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.