First Author | Simandi Z | Year | 2016 |
Journal | Mol Cell | Volume | 63 |
Issue | 4 | Pages | 647-661 |
PubMed ID | 27499297 | Mgi Jnum | J:249128 |
Mgi Id | MGI:6094116 | Doi | 10.1016/j.molcel.2016.06.039 |
Citation | Simandi Z, et al. (2016) OCT4 Acts as an Integrator of Pluripotency and Signal-Induced Differentiation. Mol Cell 63(4):647-661 |
abstractText | 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 beta-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. |