Department of Pluripotent Stem Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Department of Functional Genome Informatics, Division of Medical Genomics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Genes Cells. 2023 Dec;28(12):831-844. doi: 10.1111/gtc.13070. Epub 2023 Oct 1.
Mouse ES cell populations contain a minor sub-population that expresses genes specifically expressed in 2-cell stage embryos. This sub-population consists of 2-cell-gene labeled cells (2CLCs) generated by the transient activation of the 2-cell specific genes initiated by the master regulator, Dux. However, the mechanism regulating the transient expression remains largely unclear. Here we reported a novel function of Zfp352, one of the 2-cell specific genes, in regulating the 2CLC sub-population. Zfp352 encodes zinc-finger transcription factor belonging to the Klf family. Dux transiently activates Zfp352 after the activation of Zscan4c in a subset of the 2CLC subpopulation. Interestingly, in the reporter assay, the transcriptional activation of Zscan4c by Dux is strongly repressed by the co-expression of Zfp352. However, the knockout of Zfp352 resulted in the repression of a subset of the 2-cell-specific genes. These data suggest the dual roles of Zfp352 in regulating the transient activation of the 2-cell-specific genes.
鼠胚胎干细胞群体中存在一个亚群,该亚群表达仅在 2 细胞期胚胎中特异性表达的基因。这个亚群由通过主调控因子 Dux 启动的 2 细胞特异性基因的短暂激活产生的 2 细胞基因标记细胞(2CLC)组成。然而,调节短暂表达的机制在很大程度上仍不清楚。在这里,我们报道了 2 细胞特异性基因之一 Zfp352 在调节 2CLC 亚群中的一个新功能。Zfp352 编码属于 Klf 家族的锌指转录因子。在一小部分 2CLC 亚群中,Dux 在激活 Zscan4c 后短暂激活 Zfp352。有趣的是,在报告基因检测中,Dux 对 Zscan4c 的转录激活被 Zfp352 的共表达强烈抑制。然而,Zfp352 的敲除导致一小部分 2 细胞特异性基因的抑制。这些数据表明 Zfp352 在调节 2 细胞特异性基因的短暂激活中具有双重作用。