OCT4 Acts as an Integrator of Pluripotency and Signal-Induced Differentiation. Academic Article uri icon

Overview

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.

publication date

  • August 4, 2016

Research

keywords

  • Cell Differentiation
  • Cell Lineage
  • Embryonic Stem Cells
  • Octamer Transcription Factor-3
  • Pluripotent Stem Cells
  • Wnt Signaling Pathway

Identity

Scopus Document Identifier

  • 84992702728

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2016.06.039

PubMed ID

  • 27499297

Additional Document Info

volume

  • 63

issue

  • 4