An Expanded Oct4 Interaction Network: Implications for Stem Cell Biology, Development, and Disease
Open accessAbstract
The transcription factor Oct4 is key in embryonic stem cell identity and reprogramming. Insight into its partners should illuminate how the pluripotent state is established and regulated. Here, we identify a considerably expanded set of Oct4-binding proteins in mouse embryonic stem cells. We find that Oct4 associates with a varied set of proteins including regulators of gene expression and modulators of Oct4 function. Half of its partners are transcriptionally regulated by Oct4 itself or other stem cell transcription factors, whereas one-third display a significant change in expression upon cell differentiation. The majority of Oct4-associated proteins studied to date show an early lethal phenotype when mutated. A fraction of the human orthologs is associated with inherited developmental disorders or causative of cancer. The Oct4 interactome provides a resource for dissecting mechanisms of Oct4 function, enlightening the basis of pluripotency and development, and identifying potential additional reprogramming factors.
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Many pioneer factors recruit chromatin remodelers.
“The mechanisms of pioneer factor action are still being established [37], but at least some of them (such as FOXA, OCT4 and SOX2/SOX11) have been shown to initiate chromatin opening by direct displacement of histones [38–41], whilst many others recruit chromatin remodelers [42–50].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [43]
The Discussion (page unavailable) reports that Oct4 copurifies with subunits of the SWI/SNF nucleosome-remodeling complex, supporting an Oct4–remodeler association. It does not show that Oct4 recruits the complex, or establish that many pioneer factors recruit chromatin remodelers. (LLM, conf=0.84)
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- Authors
- Pardo, M., Lang, B., Yu, L., Prosser, H., Bradley, A., Babu, M. M., & Choudhary, J.
- Affiliations
- Wellcome Sanger Institute (GB)
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Pardo, Mercedes
- Choudhary, Jyoti
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 6
- Issue
- 4
- Pages
- 382-395
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC2860244
- OpenAlex
- W2157243724
- Cited by
- 379
- References
- 3
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 3 · 2023: 11 · 2022: 12 · 2021: 20 · 2020: 18 · 2019: 17 · 2018: 20 · 2017: 17 · 2016: 15 · 2015: 36 · 2014: 24 · 2013: 59 · 2012: 56
- FWCI
- 22.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- Oct4, protein-protein interaction network, mouse embryonic stem cells, pluripotency, stem cell reprogramming, transcription factors, gene expression regulation, cell differentiation, developmental disorders, cancer
- MeSH terms
- Animals, Cell Differentiation, Disease, Humans, Models, Biological, Mutation, Neoplasms, Phenotype, Protein Binding, Recombinant Fusion Proteins, Transcription, Genetic, Gene Transfer Techniques, Gene Expression Regulation, Developmental, Gene Dosage, Chromosomes, Artificial, Bacterial, Octamer Transcription Factor-3, Mice, Embryonic Stem Cells
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