LONGECITY

http://www.cell.com/...2765(16)30327-6

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Highlights

    •OCT4 occupies differentiation-related and low-accessible genomic regions in ESCs
    •OCT4 positively controls the level of RARγ
    •Loss of OCT4 causes dysregulation of tissue-specific RA and WNT/β-catenin response
    •Overexpression of OCT4 is sufficient to reprogram a cell type-specific signal response

Summary

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.

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