An Oct4-Centered Protein Interaction Network in Embryonic Stem Cells

Debbie van den Berg, T (Tim) Snoek, NP Mullin, A Yates, Karel Bezstarosti, Jeroen Demmers, I Chambers, Raymond Poot

Research output: Contribution to journalArticleAcademic

428 Citations (Scopus)


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.
Original languageUndefined/Unknown
Pages (from-to)369-381
Number of pages13
JournalCell Stem Cell
Issue number4
Publication statusPublished - 2010

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