Evidence map›Paper›PMID 28007765›Full record

ArticleEMBO reports2017

Changing POU dimerization preferences converts Oct6 into a pluripotency inducer.

Stepan Jerabek, Calista Kl Ng, Guangming Wu, Marcos J Arauzo-Bravo, Kee-Pyo Kim, Daniel Esch, Vikas Malik, Yanpu Chen, Sergiy Velychko, Caitlin M MacCarthy and 4 more

Open access · hybridAbstract read
In one paragraph

Article in EMBO reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

32 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
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  5. Zoological research · 2022
    Article
  6. SOX9 and SOX10 control fluid homeostasis in the inner ear for hearing through independent and cooperative mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
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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

14 authors at 5 institutions in 4 countries.

Stepan JerabekMax Planck Institute for Molecular Biomedicine, Münster, Germany.ORCID 0000-0002-3902-1939
Calista Kl NgInstitute of Medical Biology, Singapore City, Singapore.
Guangming WuMax Planck Institute for Molecular Biomedicine, Münster, Germany.
Marcos J Arauzo-BravoBiodonostia Health Research Institute, San Sebastián, Spain.
Kee-Pyo KimMax Planck Institute for Molecular Biomedicine, Münster, Germany.
Daniel EschMax Planck Institute for Molecular Biomedicine, Münster, Germany.
Vikas MalikGenome Regulation Laboratory, Drug Discovery Pipeline, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Yanpu ChenGenome Regulation Laboratory, Drug Discovery Pipeline, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Sergiy VelychkoMax Planck Institute for Molecular Biomedicine, Münster, Germany.
Caitlin M MacCarthyMax Planck Institute for Molecular Biomedicine, Münster, Germany.
Xiaoxiao YangGenome Regulation Laboratory, Drug Discovery Pipeline, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Vlad CojocaruMax Planck Institute for Molecular Biomedicine, Münster, Germany.
Hans R SchölerMax Planck Institute for Molecular Biomedicine, Münster, Germany office@mpi-muenster.mpg.de ralf@gibh.ac.cn.
Ralf JauchGenome Regulation Laboratory, Drug Discovery Pipeline, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China office@mpi-muenster.mpg.de ralf@gibh.ac.cn.ORCID 0000-0002-6590-9579
Max Planck Institute for Molecular Biomedicine · DEChinese Academy of Sciences · CNUniversity of Münster · DEIkerbasque · ESInstitute of Medical Biology · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The transcription factor Oct4 is a core component of molecular cocktails inducing pluripotent stem cells (iPSCs), while other members of the POU family cannot replace Oct4 with comparable efficiency. Rather, group III POU factors such as Oct6 induce neural lineages. Here, we sought to identify molecular features determining the differential DNA-binding and reprogramming activity of Oct4 and Oct6. In enhancers of pluripotency genes, Oct4 cooperates with Sox2 on heterodimeric SoxOct elements. By re-analyzing ChIP-Seq data and performing dimerization assays, we found that Oct6 homodimerizes on palindromic OctOct more cooperatively and more stably than Oct4. Using structural and biochemical analyses, we identified a single amino acid directing binding to the respective DNA elements. A change in this amino acid decreases the ability of Oct4 to generate iPSCs, while the reverse mutation in Oct6 does not augment its reprogramming activity. Yet, with two additional amino acid exchanges, Oct6 acquires the ability to generate iPSCs and maintain pluripotency. Together, we demonstrate that cell type-specific POU factor function is determined by select residues that affect DNA-dependent dimerization.

Indexed as

Protein MultimerizationAmino Acid SubstitutionAnimalsBinding SitesCell LineCell TransdifferentiationCellular ReprogrammingEmbryonic Stem CellsEnhancer Elements, GeneticEpigenesis, GeneticHumansInduced Pluripotent Stem CellsMiceModels, MolecularNucleotide MotifsOctamer Transcription FactorsOctamer Transcription FactorsOrganic Cation Transport ProteinsPOU Domain FactorsSLC22A16 protein, humanDNA bindingOct4POU factorsreprogramming to pluripotency

Identifiers

PMID28007765
PMCPMC5286379
OpenAlexW2563950564

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.