GENETIC CONTROL OF HEMATOPOIETIC CELL DOFFERENTIATION

造血学是分析细胞分化调控的良好模型系统。利用这个系统，我们试图识别调节细胞分化的转录因子。我们对核因子-E2的功能及相关因素进行了分析，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)为了寻找新的核因子-E2相关转录因子，我们进行了进一步的同源筛选。结果，我们成功地鉴定了与NF-E2相关的第六个成员，我们将其命名为Nrf3。其表达谱提示Nrf3可能参与了造血细胞分化的调控。我们现在正在与Engel教授一起使用小鼠系统进行基因破坏实验。(2)通过建立Nrf2基因敲除小鼠并分析其表型变化，我们揭示了Nrf2是II期解毒系统表达的关键必需调节因子。(3)Bach1和Bach2的BTB结构域似乎参与了染色质结构的调节。利用原子力显微镜，我们揭示了Bach1，以及可能的Bach2，作为一种新型的结构转录因子，介导DNA环的形成。因此，Bach1可能参与了珠蛋白基因位点控制区的调控。

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.