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An Oct4-centered protein interaction network in embryonic stem cells.

TitleAn Oct4-centered protein interaction network in embryonic stem cells.
Publication TypeJournal Article
Year of Publication2010
Authorsvan den Berg DLC, Snoek T, Mullin NP, Yates A, Bezstarosti K, Demmers J, Chambers I, Poot RA
JournalCell Stem Cell
Date Published2010 Apr 2
KeywordsAnimals, Cell Line, Cell Proliferation, Embryonic Stem Cells, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Mass Spectrometry, Mice, Octamer Transcription Factor-3, Phenotype, Protein Binding, Protein Transport, Transcription Factors

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.

Alternate JournalCell Stem Cell
PubMed ID20362541
PubMed Central IDPMC2860243
Grant List / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom