Cited by 379Pluripotent Stem Cells ResearchDevelopmental Biology and Gene RegulationGenomics and Chromatin Dynamics

An Expanded Oct4 Interaction Network: Implications for Stem Cell Biology, Development, and Disease

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Pardo, Mercedes, Lang, Benjamin, Yu, Lu, Prosser, Haydn, Bradley, Allan, Babu, M. Madan, Choudhary, Jyoti·2010·Cell Stem Cell

Abstract

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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Cited by

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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
OpenAlex
W2157243724
Cited by
379
References
3
Citations by year
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FWCI
22.55
Type
journal article
Language
en
Open access
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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