REGULATION OF DIFFERENTIATION BY BACH TRANSCRIPTION FACTORS

为了理解细胞分化的分子调控，揭示这些过程中的转录调控是必不可少的。Bachi和Bach 2是通过与Maf家族转录因子形成异二聚体而与DNA结合的密切相关的转录因子。在过去的两年中，我们积累的结果表明，Bachi和Bach 2参与造血的调节，并且它们作为一种新型的建筑转录因子发挥作用。(1)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，fundion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。(2)Bach 2的表达对造血细胞中的B细胞具有特异性。其表达在早期阶段高，并在成熟为浆细胞时下调。Bach 2抑制免疫球蛋白重链基因的3'增强子。因此，Bach 2似乎在B细胞分化期间调节阶段特异性基因表达。(3)利用酵母双杂交筛选技术，我们分离到一个新的转录因子FOB（friend of Bach），它是一个与Bach的BTB结构域结合的蛋白。FOB携带BTB结构域以及C2 H2型Zn指。FOB基因在造血细胞中的表达谱提示它是Bach 1和/或Bach 2的配偶体。

To understand molecular regulation of cell differentiation, it is essential to reveal regulation of transcription in these processes. Bachi and Bach2 are closely related transcription factors that bind to DNA by forming heterodimers with Maf family of transcription factors. During the past two years supported by this grant, we accumulated results that suggested that Bachi and Bach2 are involved in regulation of hematopoiesis, and that they function as a novel type of architectural transcription fadors.(1) 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, fundion 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.(2) Expression of Bach2 is specific to B cells among hematopoietic cells. Its expression is high during early stages and down regulated upon maturation to plasmacytes. Bach2 represses 3' enhancer of the immunoglobulin heavy chain gene. Thus Bach2 appears to regulate stage-specific gene expression during B cell differentiation.(3) Using yeast two hybrid screen, we isolated a novel transcription factor, FOB (friend of Bach), as aprotein that binds to the BTB domain of Bach. FOB carries the BTB domain as well as a C2H2-typeZn fingers. Expression profile of FOB suggested that it is a partner of Bach1 and/or Bach2 inhematopoietic cells.