Yamaguchi Yukari, Takamura Hiroyuki, Tada Yuhki, Akagi Tadayuki, Oyama Katsunobu, Miyashita Tomoharu, Tajima Hidehiro, Kitagawa Hirohisa, Fushida Sachio, Yokota Takashi, Ohta Tetsuo, Koide Hiroshi
Department of Gastroenterologic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
Department of Gastroenterologic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
Biochem Biophys Res Commun. 2014 Oct 31;453(4):817-20. doi: 10.1016/j.bbrc.2014.10.020. Epub 2014 Oct 14.
To maintain the self-renewal of embryonic stem (ES) cells, several core transcription factors, including Oct3/4, STAT3, and Nanog, regulate the expression of their target genes. Zinc finger protein 57 (Zfp57) is specifically expressed in self-renewing ES cells and its expression level is reduced upon ES cell differentiation, suggesting that expression of this transcription factor is regulated by core transcription factors. In the present study, we investigated whether Zfp57 expression is regulated by Nanog. Nanog overexpression resulted in the upregulation of Zfp57. On the other hand, knockdown of Nanog reduced the expression level of Zfp57. In addition, we identified the Nanog-responsive region in the promoter of the Zfp57 gene. These results suggest that Nanog is an upstream regulator of Zfp57. Moreover, Nanog overexpression promoted the growth of ES cells in soft agar and this was suppressed by Zfp57 knockdown, suggesting that the Nanog/Zfp57 pathway plays a central role in anchorage-independent growth of ES cells. Interestingly, NANOG overexpression also led to the upregulation of ZFP57 in two human tumor cell lines. Taken together, our results suggest that Nanog positively regulates Zfp57 expression in multiple types of cells.
为维持胚胎干细胞（ES细胞）的自我更新，包括Oct3/4、STAT3和Nanog在内的几种核心转录因子调控其靶基因的表达。锌指蛋白57（Zfp57）在自我更新的ES细胞中特异性表达，且其表达水平在ES细胞分化时降低，这表明该转录因子的表达受核心转录因子调控。在本研究中，我们调查了Zfp57的表达是否受Nanog调控。Nanog过表达导致Zfp57上调。另一方面，敲低Nanog降低了Zfp57的表达水平。此外，我们在Zfp57基因启动子中鉴定出Nanog反应区域。这些结果表明Nanog是Zfp57的上游调节因子。此外，Nanog过表达促进了ES细胞在软琼脂中的生长，而这被Zfp57敲低所抑制，表明Nanog/Zfp57途径在ES细胞的非锚定依赖性生长中起核心作用。有趣的是，NANOG过表达在两种人类肿瘤细胞系中也导致ZFP57上调。综上所述，我们的结果表明Nanog在多种类型细胞中正向调控Zfp57的表达。
