GENETIC CONTROL OF HEMATOPOIETIC CELL DOFFERENTIATION

造血是分析细胞分化调控的良好模型系统。使用这个系统，我们试图确定调节细胞分化的转录因子。我们分析了NF-E2的功能及其相关因素，积累了新的和意想不到的结果。这些发现将有助于理解造血的分子和遗传调控。(1)为了鉴定新的NF-E2相关转录因子，我们进行了进一步的同源性筛选。结果，我们成功地鉴定了NF-E2相关因子的第六个成员，我们将其命名为Nrf 3。其表达谱提示Nrf 3可能调控造血细胞的分化。目前我们正在与Engel教授合作，利用小鼠系统进行基因中断实验。(2)通过构建nrf 2基因敲除小鼠模型并分析其表型变化，我们发现Nrf 2是II相去铁蛋白系统表达的关键必需调节因子。(3)Bach 1和Bach 2的BTB结构域似乎参与调节染色质结构。使用原子力显微镜，我们发现，巴赫1，可能巴赫2，功能作为一种新型的建筑转录因子，介导DNA环的形成。因此，Bach 1可能参与调节球蛋白基因座控制区。

Hematopoiesis is a good model system for analyzing regulation of cell differentiation. Using this system, we tried to identify transcription factors that regulate cell differentiation. We analyzed function of NF-E2 and related factors, and accumulated novel as well as unexpected results. These findings should lead to understanding of molecular and genetic regulation of hematopoiesis.(1) To identify novel NF-E2-related transcription factors, we carried out further homology screening. As a result, we succeeded in identifying sixth member of the NF-E2-related factors which we named Nrf3. Its expression profile suggested that Nrf3 may regulate differentiation of hematopoietic cell differentiation. We are now carrying out gene disruption experiment using mice system, together with Prof.Engel.(2) By making nrf2-knockout mice and analyzing its phenotypic changes, we revealed that Nrf2 is a key essentail regulator of phase II de-toxifying system expression.(3) The BTB domain of Bach1 and Bach2 appears to be involved in regulation of chromatin structure. Using atomic force microscopy, we revealed that Bach1, and possible Bach2, function as a novel type of architectural transcription factor that mediate DNA loop formation. As such, Bach1 may be involved in regulation of the globin gene locus control region.