Yu Hong-bing, Kunarso Galih, Hong Felicia Huimei, Stanton Lawrence W
Department of Biological Sciences, National University of Singapore, Singapore 117542, Singapore.
J Biol Chem. 2009 Nov 6;284(45):31327-35. doi: 10.1074/jbc.M109.016162. Epub 2009 Sep 9.
Zfp206 (recently renamed Zscan10) encodes a zinc finger transcription factor specifically expressed in human and mouse embryonic stem cells (ESC). It has been shown that Zfp206 is required to maintain ESC in an undifferentiated, pluripotent state. Presented here are data showing that Zfp206 works together with two other transcription factors, Oct4 and Sox2, which are also essential regulators of ESC pluripotency. We show that Zfp206 binds to the Oct4 promoter and directly regulates Oct4 expression. Genome-wide mapping of Zfp206-binding sites in ESC identifies more than 3000 target genes, many of which encode transcription factors that are also targeted for regulation by Oct4 and Sox2. In addition, we show that Zfp206 physically interacts with both Oct4 and Sox2. These data demonstrate that Zfp206 is a key component of the core transcriptional regulatory network and together with Oct4 and Sox2 regulates differentiation of ESC.
Zfp206(最近更名为Zscan10)编码一种锌指转录因子,该因子在人类和小鼠胚胎干细胞(ESC)中特异性表达。研究表明,Zfp206是维持胚胎干细胞处于未分化的多能状态所必需的。本文展示的数据表明,Zfp206与另外两个转录因子Oct4和Sox2共同发挥作用,这两个转录因子也是胚胎干细胞多能性的重要调节因子。我们发现Zfp206结合到Oct4启动子上并直接调节Oct4的表达。对胚胎干细胞中Zfp206结合位点进行全基因组定位,鉴定出3000多个靶基因,其中许多基因编码的转录因子也是Oct4和Sox2的调控靶点。此外,我们还发现Zfp206与Oct4和Sox2都存在物理相互作用。这些数据表明,Zfp206是核心转录调控网络的关键组成部分,与Oct4和Sox2一起调节胚胎干细胞的分化。