c-Jun as a one-way valve at the naive to primed interface

Authors：Li, Dongwei^*; Luo, Ling; Guo, Lin; Wu, Chuman; Zhang, Ran; Peng, Yuling; Wu, Menghua; Kuang, Junqi; Li, Yan; Zhang, Yudan; Xie, Jun; Xie, Wenxiu; Mao, Rui; Ma, Gang; Fu, Xiuling; Chen, Jiekai; Hutchins, Andrew P.; Pei, Duanqing^*

Source：Cell and Bioscience, 2023, 13(1): 191.

DOI：10.1186/s13578-023-01141-0

• EpiSCs
• c-Jun
• Naive to primed transition
• Primed to naive transition

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.

• Institution
  5; 广东省人民医院; 中国科学院; 广州医学院; 广东省心血管病研究所; 南方医科大学