OCT4 Acts as an Integrator of Pluripotency and Signal-Induced Differentiation

Zoltan Simandi, Attila Horvath, Lyndsey C. Wright, Ixchelt Cuaranta-Monroy, Isabella De Luca, Katalin Karolyi, Sascha Sauer, Jean Francois Deleuze, Lorraine J. Gudas, Shaun M. Cowley, Laszlo Nagy

Research output: Article

31 Citations (Scopus)

Abstract

Cell type specification relies on the capacity of undifferentiated cells to properly respond to specific differentiation-inducing signals. Using genomic approaches along with loss- and gain-of-function genetic models, we identified OCT4-dependent mechanisms that provide embryonic stem cells with the means to customize their response to external cues. OCT4 binds a large set of low-accessible genomic regions. At these sites, OCT4 is required for proper enhancer and gene activation by recruiting co-regulators and RAR:RXR or β-catenin, suggesting an unexpected collaboration between the lineage-determining transcription factor and these differentiation-initiating, signal-dependent transcription factors. As a proof of concept, we demonstrate that overexpression of OCT4 in a kidney cell line is sufficient for signal-dependent activation of otherwise unresponsive genes in these cells. Our results uncover OCT4 as an integral and necessary component of signal-regulated transcriptional processes required for tissue-specific responses.

Original languageEnglish
Pages (from-to)647-661
Number of pages15
JournalMolecular Cell
Volume63
Issue number4
DOIs
Publication statusPublished - aug. 18 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Simandi, Z., Horvath, A., Wright, L. C., Cuaranta-Monroy, I., De Luca, I., Karolyi, K., Sauer, S., Deleuze, J. F., Gudas, L. J., Cowley, S. M., & Nagy, L. (2016). OCT4 Acts as an Integrator of Pluripotency and Signal-Induced Differentiation. Molecular Cell, 63(4), 647-661. https://doi.org/10.1016/j.molcel.2016.06.039