An Oct4-Centered Protein Interaction Network in Embryonic Stem Cells
Open accessAbstract
Transcription factors, such as Oct4, are critical for establishing and maintaining pluripotent cell identity. Whereas the genomic locations of several pluripotency transcription factors have been reported, the spectrum of their interaction partners is underexplored. Here, we use an improved affinity protocol to purify Oct4-interacting proteins from mouse embryonic stem cells (ESCs). Subsequent purification of Oct4 partners Sall4, Tcfcp2l1, Dax1, and Esrrb resulted in an Oct4 interactome of 166 proteins, including transcription factors and chromatin-modifying complexes with documented roles in self-renewal, but also many factors not previously associated with the ESC network. We find that Esrrb associated with the basal transcription machinery and also detect interactions between transcription factors and components of the TGF-beta, Notch, and Wnt signaling pathways. Acute depletion of Oct4 reduced binding of Tcfcp2l1, Dax1, and Esrrb to several target genes. In conclusion, our purification protocol allowed us to bring greater definition to the circuitry controlling pluripotent cell identity.
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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 [44]
The Results (An Oct4-Centered Interaction Network; page not provided) report that several embryonic-stem-cell transcription factors associate with chromatin-modifying complexes, including SWI/SNF. The Discussion (Multiple Network Connections with Chromatin- and Protein-Modifying Factors; page not provided) proposes that recruitment may occur through initial local targeting, but does not establish that many pioneer factors recruit remodelers. The claim presents that proposed mechanism as a demonstrated, broader finding. (LLM, conf=0.86)
Experimental — accuracy not yet measuredGFP-MBD3 affinity purification identified known NuRD core subunits and previously described interactors ZMYND8, ZNF592, and SALL4.
“In each of these pulldowns, known NuRD core subunits were identified. In addition, several previously described NuRD interactors were detected, including ZMYND8, ZNF592, and SALL4 [8,14,17].”
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- Authors
- van den Berg, D. L. C., Snoek, T., Mullin, N. P., Yates, A., Bezstarosti, K., Demmers, J., Chambers, I., & Poot, R. A.
- Affiliations
- Erasmus MC (NL)
- MRC Centre for Regenerative Medicine (GB)
- Corresponding author
- Poot, Raymond A.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 6
- Issue
- 4
- Pages
- 369-381
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC2860243
- OpenAlex
- W2147231609
- Cited by
- 542
- References
- 57
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 10 · 2023: 13 · 2022: 16 · 2021: 26 · 2020: 31 · 2019: 32 · 2018: 28 · 2017: 26 · 2016: 34 · 2015: 57 · 2014: 48 · 2013: 63 · 2012: 67
- FWCI
- 26.07
- 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)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Funders
- Wellcome Trust
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Medical Research Council
- 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, SALL4, DAX-1, ESRRB, basal transcription machinery, TGF-beta signaling, Notch signaling, Wnt signaling, transcription factor binding, self-renewal
- MeSH terms
- Animals, Cell Line, Phenotype, Protein Binding, Mass Spectrometry, Transcription Factors, Gene Expression Regulation, Developmental, Protein Transport, Cell Proliferation, Octamer Transcription Factor-3, Mice, Gene Regulatory Networks, Embryonic Stem Cells
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