Klf4 could be activated by Pou5f3/Stat3 to induce the expression of Nanog in Japanese flounder
Klf4 could be activated by Pou5f3/Stat3 to induce the expression of Nanog in Japanese flounder
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Pou5f3/Stat3激活Klf4诱导牙鲆Nanog表达
DOI：
10.1016/j.gene.2018.11.029
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发表时间：
2019
期刊：
影响因子：
3.5
通讯作者：
Zhang Quanqi
中科院分区：
文献类型：
--
作者：
Sun Yan;Liu Jinxiang;Wang Bo;Liu Xiumei;Du Xinxin;Liu Yuxiang;Zhang Quanqi
Krüppel样因子4（Klf4）是KLF家族的一种锌指蛋白转录因子，在细胞增殖、分化、胚胎发育和肿瘤形成等重要生物学过程中发挥重要作用。本研究对牙鲆Klf4基因的cDNA全序列进行了分析。系统发育、基因结构和同线性分析表明，PoKlf4与硬骨鱼属的PoKlf4基因保守。PoKlf4在胚胎发育早期表达量较高，但在原肠胚形成开始时表达量降低，提示其可能参与胚胎发育。组织表达谱显示PoKlf4在卵巢中的表达高于睾丸。原位杂交结果显示，PoKlf4在精原细胞、卵母细胞和卵原细胞中也有表达，在鳃上皮细胞和板层上皮细胞中也有高水平表达。PoKlf4基因启动子的功能研究为理解PoKlf4基因的分子调控机制提供了有价值的信息。PoKlf4可上调阻止ES细胞分化的基因Nanog，并被维持ES细胞自我更新的Pou5f3和Stat3基因上调。这些结果表明PoKlf4维持了ES细胞的多能性。本研究为探索PoKlf4的调控网络提供了有价值的信息，并为进一步研究该基因的功能奠定了基础。
Krüppel-like factor 4 (Klf4) is a zinc finger protein transcription factor of the KLF family and plays an important role in various important biological process, including cell proliferation, differentiation, embryonic development, and cancer formation. In this study, the full lengthKlf4cDNA sequence of Japanese flounder (Paralichthys olivaceus) was analyzed. Phylogenetic, gene structure, and synteny analysis revealed thatPoKlf4was conserved to that of teleost. Transcript ofPoKlf4showed that its expression was high during early embryonic development but reduced when gastrulation began, thus indicating its possible role in embryonic development. Tissue expression pattern showed thatPoKlf4was expressed higher in ovaries than in testes. ISH revealed thatPoKlf4was also expressed in spermatogonium, oocytes, and oogonia and in high levels in epithelial and lamellar epithelial cells of gills. Functional characterization ofPoKlf4gene promoter provided valuable information in understanding the molecular regulatory mechanisms ofPoKlf4gene. PoKlf4 could up-regulateNanog, a gene that prevents ES cells from differentiating and being up-regulated byPou5f3andStat3genes that could maintain ES cell self-renewal. These results suggested thatPoKlf4maintains the pluripotency of ES cells. This study provides valuable information in exploring the regulatory network ofPoKlf4and lays the foundation for further research on the function of this gene.