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OCT4 acts as an integrator of pluripotency and signal-induced differentiation

Item Type:Article
Title:OCT4 acts as an integrator of pluripotency and signal-induced differentiation
Creators Name:Simandi, Z. and Horvath, A. and Wright, L.C. and Cuaranta-Monroy, I. and De Luca, I. and Karolyi, K. and Sauer, S. and Deleuze, J.F. and Gudas, L.J. and Cowley, S.M. and Nagy, L.
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 {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.
Keywords:Binding Sites, Cell Differentiation, Cell Lineage, Cellular Reprogramming, Embryonic Stem Cells, Gene Expression Regulation, Genetic Promoter Regions, Genetic Transcription, HEK293 Cells, Homeodomain Proteins, Octamer Transcription Factor-3, Pluripotent Stem Cells, RNA Interference, Retinoic Acid Receptor alpha, Retinoid X Receptors, Transfection, Tretinoin, Wnt Signaling Pathway, Animals, Mice
Source:Molecular Cell
ISSN:1097-2765
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:63
Number:4
Page Range:647-661
Date:18 August 2016
Official Publication:https://doi.org/10.1016/j.molcel.2016.06.039
PubMed:View item in PubMed

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