An Oct4-Centered Protein Interaction Network in Embryonic Stem Cells

Adam Yates, Debbie L.C. van den Berg, Tim Snoek, Nick P. Mullin, Karel Bezstarosti, Jeroen Demmers, Ian Chambers, Raymond A. Poot

Research output: Contribution to journalArticle

366 Citations (Scopus)

Abstract

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-β, 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.

Original languageEnglish
Pages (from-to)369-381
Number of pages13
JournalCell Stem Cell
Volume6
Issue number4
DOIs
Publication statusPublished - 2 Apr 2010
Externally publishedYes

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Protein Interaction Maps
Embryonic Stem Cells
Transcription Factors
Wnt Signaling Pathway
Chromatin
Proteins

Cite this

Yates, A., van den Berg, D. L. C., Snoek, T., Mullin, N. P., Bezstarosti, K., Demmers, J., ... Poot, R. A. (2010). An Oct4-Centered Protein Interaction Network in Embryonic Stem Cells. Cell Stem Cell, 6(4), 369-381. https://doi.org/10.1016/j.stem.2010.02.014
Yates, Adam ; van den Berg, Debbie L.C. ; Snoek, Tim ; Mullin, Nick P. ; Bezstarosti, Karel ; Demmers, Jeroen ; Chambers, Ian ; Poot, Raymond A. / An Oct4-Centered Protein Interaction Network in Embryonic Stem Cells. In: Cell Stem Cell. 2010 ; Vol. 6, No. 4. pp. 369-381.
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Yates, A, van den Berg, DLC, Snoek, T, Mullin, NP, Bezstarosti, K, Demmers, J, Chambers, I & Poot, RA 2010, 'An Oct4-Centered Protein Interaction Network in Embryonic Stem Cells', Cell Stem Cell, vol. 6, no. 4, pp. 369-381. https://doi.org/10.1016/j.stem.2010.02.014

An Oct4-Centered Protein Interaction Network in Embryonic Stem Cells. / Yates, Adam; van den Berg, Debbie L.C.; Snoek, Tim; Mullin, Nick P.; Bezstarosti, Karel; Demmers, Jeroen; Chambers, Ian; Poot, Raymond A.

In: Cell Stem Cell, Vol. 6, No. 4, 02.04.2010, p. 369-381.

Research output: Contribution to journalArticle

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Yates A, van den Berg DLC, Snoek T, Mullin NP, Bezstarosti K, Demmers J et al. An Oct4-Centered Protein Interaction Network in Embryonic Stem Cells. Cell Stem Cell. 2010 Apr 2;6(4):369-381. https://doi.org/10.1016/j.stem.2010.02.014