Elucidation of the molecular mechanism by which NR5A family induces ovarian differentiation

我们在转录起始位点上游约3000 bp的人类StAR基因中发现了新的SF-1/LRH-1结合位点。我们通过荧光素酶报告系统证明了上游区域对基因表达的激活是重要的。有趣的是，通过ChIP实验，在SF-1/LRH-1结合位点（启动子和增强子区域）发现核小体排出。3C分析显示，在启动子和增强子区域之间形成了DNA环。这些结果表明，新的增强子区域通过协调染色质环结构参与了人类StAR基因的激活。此外，我们通过生化方法鉴定了转录因子C/EBPβ，该因子被鉴定为SF-1复合物的一个组成部分。我们发现C/EBPβ在SF-1/ lrh -1诱导的卵巢分化中也很重要。

We identified novel SF-1/LRH-1 binding sites in human StAR gene about 3,000 bp upstream from the transcriptional start site. We demonstrated by a luciferase reporter system that the upstream region was important for the activation of gene expression. Interestingly, nucleosome eviction has been found at those SF-1/LRH-1 binding sites (both promoter and enhancer region) by ChIP assay. 3C analysis revealed that DNA loop was formed between the promoter and the enhancer regions. These results indicate that the novel enhancer region participates in the human StAR gene activation by orchestrating chromatin loop architecture. Furthermore, we characterized transcription factor C/EBPβ which is identified as one of the components of SF-1 complex by biochemical approach. We elucidated C/EBPβ is also important for SF-1/LRH-1-induced ovarian differentiation as a these partner.