Asaka Masamitsu N, Uranishi Kousuke, Suzuki Ayumu, Hirasaki Masataka, Nishimoto Masazumi, Okuda Akihiko
Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama, 350-1241, Japan.
Dev Growth Differ. 2017 Oct;59(8):639-647. doi: 10.1111/dgd.12403. Epub 2017 Oct 2.
The Oct4 gene is a master regulator of the pluripotent properties of embryonic stem cells (ESCs). Recently, Oct4 loci were shown to frequently localize in close proximity to one another during the early stage of cellular differentiation, implicating this event as an important prerequisite step for ESCs to exert their full differentiation potential. Although the differentiation capacity of embryonal carcinoma cells (ECCs), such as F9 and P19 ECC lines, is severely restricted compared with ESCs, ECCs bear a highly similar expression profile to that of ESCs including expression of Oct4 and other pluripotency marker genes. Therefore, we examined whether allelic pairing of Oct4 loci also occurs during differentiation of F9 and P19 ECCs. Our data clearly demonstrate that this event is only observed within ESCs, but not ECCs, subjected to induction of differentiation, indicating transient allelic pairing of Oct4 loci as a specific feature of pluripotent ESCs. Moreover, our data revealed that this pairing did not occur broadly across chromosome 17, which carries the Oct4 gene, but occurred locally between Oct4 loci, suggesting that Oct4 loci somehow exert a driving force for their allelic pairing.
Oct4基因是胚胎干细胞（ESC）多能特性的主要调节因子。最近研究表明，在细胞分化早期，Oct4基因座经常彼此紧密定位，这意味着该事件是ESC发挥其完全分化潜能的重要前提步骤。尽管与ESC相比，胚胎癌细胞（ECC）如F9和P19 ECC系的分化能力受到严重限制，但ECC与ESC具有高度相似的表达谱，包括Oct4和其他多能性标记基因的表达。因此，我们研究了Oct4基因座的等位基因配对是否也发生在F9和P19 ECC的分化过程中。我们的数据清楚地表明，仅在接受分化诱导的ESC中观察到该事件，而在ECC中未观察到，这表明Oct4基因座的瞬时等位基因配对是多能ESC的一个特定特征。此外，我们的数据显示，这种配对并非在携带Oct4基因的17号染色体上广泛发生，而是在Oct4基因座之间局部发生，这表明Oct4基因座以某种方式为其等位基因配对施加了驱动力。
