School of Chemical Engineering and Physical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India.
Department of Chemistry, National University of Singapore, Singapore.
Biochem J. 2018 Mar 20;475(6):1075-1089. doi: 10.1042/BCJ20170418.
Oct4 and Sox2 regulate the expression of target genes such as , and , by binding to their respective regulatory motifs. Their functional cooperation is reflected in their ability to heterodimerize on adjacent regulatory motifs, the composite Sox/Oct motif. Given that Oct4 and Sox2 regulate many developmental genes, a quantitative analysis of their synergistic action on different Sox/Oct motifs would yield valuable insights into the mechanisms of early embryonic development. In the present study, we measured binding affinities of Oct4 and Sox2 to different Sox/Oct motifs using fluorescence correlation spectroscopy. We found that the synergistic binding interaction is driven mainly by the level of Sox2 in the case of the Sox/Oct motif. Taking into account expression levels fluctuate more than , our finding provides an explanation on how Sox2 controls the segregation of the epiblast and primitive endoderm populations within the inner cell mass of the developing rodent blastocyst.
Oct4 和 Sox2 通过与各自的调控基序结合，调节靶基因的表达，如 、 等。它们的功能合作反映在它们能够在相邻的调控基序（复合 Sox/Oct 基序）上形成异二聚体。鉴于 Oct4 和 Sox2 调节许多发育基因，对它们在不同 Sox/Oct 基序上的协同作用进行定量分析，将为早期胚胎发育的机制提供有价值的见解。在本研究中，我们使用荧光相关光谱法测量了 Oct4 和 Sox2 与不同 Sox/Oct 基序的结合亲和力。我们发现，在 Sox/Oct 基序的情况下，协同结合相互作用主要由 Sox2 的水平驱动。考虑到 的表达水平波动比 更大，我们的发现提供了一种解释，说明 Sox2 如何控制发育中的啮齿动物囊胚内细胞团中内胚层和原始内胚层群体的分离。
