Tomioka Mizuho, Nishimoto Masazumi, Miyagi Satoru, Katayanagi Tomoko, Fukui Nobutaka, Niwa Hitoshi, Muramatsu Masami, Okuda Akihiko
Division of Developmental Biology, Saitama Medical School Research Center for Genomic Medicine, 1397-1 Yamane Hidaka-City, Saitama 350-1241, Japan.
Nucleic Acids Res. 2002 Jul 15;30(14):3202-13. doi: 10.1093/nar/gkf435.
Sox-2 is a transcriptional cofactor expressed in embryonic stem (ES) cells as well as in neuronal cells. It has been demonstrated that Sox-2 plays an important role in supporting gene expression in ES cells, especially by forming a complex with embryonic Octamer factor, Oct-3/4. Here, we have analyzed the regulatory regions of the Sox-2 gene and identified two enhancers which stimulate transcription in ES cells as well as in embryonal carcinoma cells. These regulatory regions, which we termed Sox regulatory regions (SRR) 1 and 2, exert their function specifically when cells are in an undifferentiated state. Interestingly, like the regulatory elements of FGF-4 and UTF1 genes, combinatorial action of Octamer and Sox-2 binding sites support the SRR2 activity. However, biochemical analyses reveal that, due to the unique sequence and/or its organization, the SRR2 bears distinct characteristics from those of FGF-4 and UTF1 regulatory elements. That is, unlike the FGF-4 gene enhancer, the SRR2 precludes the binding of the Oct-1-Sox-2 complex. The difference between the SRR2 and UTF1 regulatory element is in the ability of SRR2 to recruit the Oct-6-Sox-2 complex as well as the Oct-3/4-Sox-2 complex. Co-transfection analyses confirm that both complexes are able to stimulate transcription through the SRR2 element.
Sox-2是一种转录辅因子，在胚胎干细胞（ES细胞）以及神经细胞中表达。已经证明，Sox-2在支持ES细胞中的基因表达方面发挥重要作用，特别是通过与胚胎八聚体因子Oct-3/4形成复合物来实现。在这里，我们分析了Sox-2基因的调控区域，并鉴定出两个增强子，它们在ES细胞和胚胎癌细胞中均能刺激转录。我们将这些调控区域称为Sox调控区域（SRR）1和2，它们在细胞处于未分化状态时特异性地发挥功能。有趣的是，与FGF-4和UTF1基因的调控元件一样，八聚体和Sox-2结合位点的组合作用支持SRR2的活性。然而，生化分析表明，由于其独特的序列和/或组织方式，SRR2具有与FGF-4和UTF1调控元件不同的特征。也就是说，与FGF-4基因增强子不同，SRR2阻止Oct-1-Sox-2复合物的结合。SRR2与UTF1调控元件的区别在于SRR2募集Oct-6-Sox-2复合物以及Oct-3/4-Sox-2复合物的能力。共转染分析证实，这两种复合物都能够通过SRR2元件刺激转录。
