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
Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, 190 Kaiyuan Dadao, Huangpu District, Guangzhou, 510799, China.
Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Lineage and Development, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
Cell Biosci. 2023 Oct 14;13(1):191. doi: 10.1186/s13578-023-01141-0.
c-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.
Here, we show that c-Jun acts as a one-way valve to preserve the primed state and impair reversion to the naïve 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 naïve 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 naïve-specific enhancers. When the primed cells are induced to reprogram to a naïve state, these enhancers are more rapidly activated when c-Jun is lost or impaired, and the conversion is more efficient.
The 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.
c-Jun是一种原癌基因，在许多生理和病理条件下，特别是在体细胞中，作为转录因子发挥作用以激活基因表达。然而，其在早期胚胎发育中的作用仍不清楚。
在此，我们表明c-Jun作为一个单向阀来维持启动状态并损害向原始状态的逆转。c-Jun在从原始状态到启动状态的转变过程中被诱导，它作用于稳定染色质结构并抑制逆向转变。c-Jun的缺失对从原始状态到启动状态的转变几乎没有影响，对启动细胞也没有表型效应，然而，在启动细胞中，c-Jun的缺失导致未能正确关闭原始特异性增强子。当启动细胞被诱导重编程为原始状态时，当c-Jun缺失或受损时，这些增强子会更快地被激活，并且转化更有效。
本研究结果表明，c-Jun可以作为启动态上胚层干细胞中的染色质稳定剂，维持表观遗传细胞类型状态，并作为细胞命运转换的单向阀。
