Journal
CELL AND BIOSCIENCE
Volume 13, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13578-023-01141-0
Keywords
EpiSCs; c-Jun; Naive to primed transition; Primed to naive transition
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The study finds that c-Jun functions as a one-way valve in embryonic stem cells, preserving the primed state and preventing reversion to the naive state. It stabilizes the chromatin structure and inhibits the reverse transition. Loss or impairment of c-Jun accelerates the activation of naive-specific enhancers and enhances the efficiency of cell fate conversion.
Backgroundc-Jun is a proto-oncogene functioning as a transcription factor to activate gene expression under many physiological and pathological conditions, particularly in somatic cells. However, its role in early embryonic development remains unknown.ResultsHere, we show that c-Jun acts as a one-way valve to preserve the primed state and impair reversion to the naive state. c-Jun is induced during the naive to primed transition, and it works to stabilize the chromatin structure and inhibit the reverse transition. Loss of c-Jun has surprisingly little effect on the naive to primed transition, and no phenotypic effect on primed cells, however, in primed cells the loss of c-Jun leads to a failure to correctly close naive-specific enhancers. When the primed cells are induced to reprogram to a naive state, these enhancers are more rapidly activated when c-Jun is lost or impaired, and the conversion is more efficient.ConclusionsThe results of this study indicate that c-Jun can function as a chromatin stabilizer in primed EpiSCs, to maintain the epigenetic cell type state and act as a one-way valve for cell fate conversions.
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